315
consumption of more fruits, vegetables, and grains, but fewer high-fat meat and dairy foods.6 By USA standards (163-5 g fat daily and 115-6 kg alcohol per year in 1986-881), the French food supply is quite healthy, but it is changing rapidly and for the worse. If current trends continue, one of the world’s most elegant and healthy cuisines-and the "French paradox"-will be lost forever. Neither gourmands nor cardiologists should remain complacent. Department of Nutrition, Food, and Hotel Management, New York University, New York, NY 10003 USA
MARION NESTLE
1. Food and
Agriculture Organisation. FAO food balance sheets, 1984-86 average. Rome: Food and Agriculture Organisation, 1991. 2. Putnam JJ, Allshouse JE. Food consumption, prices, and expenditures, 1968-89. Washington, DC: US Department of Agriculture, May, 1991. 3. US Department of Agriculture. Nutrient content of the USA food supply. HNIS Adm Rep No 299-21. Hyattsville, MD: US Department of Agriculture, August, 1988. 4. Spiller GA, ed. The Mediterranean diets in health and disease. New York: AVI/Van Nostrand Reinhold, 1991. 5. Aigrain P, Boulet D, Lambert JL, Laporte JP. La consommation du vin en France en 1990: evolution 1980-90—projections 1995-2000. Montpellier: Office National Interprofessionnel des Vins, Institut National de la Recherche Agronomique, September, 1991. 6. World Health Organisation. Diet, nutrition, and the prevention of chronic diseases. WHO Tech Rep Series 797. Geneva: World Health Organisation, 1990.
"Herd
immunity" and the meningococcal vaccine trial in Norway
SiR,—"Herd immunity" might explain! the result of our trial against serogroup B meningococcal disease in secondary schoolchildren which was randomised at school level Z If the vaccine protected the individual not only against invasive disease but also against carriage, the risk of infection in "vaccinated
protection
schools" would be less than in "placebo schools". Herd immunity will increase recorded efficacy if the randomised groups can be considered as largely separate populations with a high rate of internal meningococcal exchange. Consequently, the chance of revealing any efficacy will be reduced if individual randomisation is used. A 100% prevention of carriage would theoretically reduce the risk of infection for the non-volunteers proportionately to the percentage of vaccinees in the schools. At the start of the trial the incidence of meningococcal B disease in secondary schoolchildren in Norway was about 15/100 000; the total number of secondary school students was only 235 000. Even with a very high rate of volunteering and with a vaccine efficacy that did not decrease for five or six years, an individual-randomised experiment would have had slight chance of being conclusive. The efficacy calculated was the sum of direct and indirect protective efficacy, as Fine correctly pointed out.! The question is whether indirect protection with our vaccine is likely and if we have seen such an effect. In several phase II studies with pharyngeal swabs we found no evidence that vaccination significantly prevents acquisition of meningococcal carriage. Neither was the carriage terminated in a substantial number of those who were carriers at vaccination. These studies, however, do not exclude a more subtle effect on carriage. The frequency of carriage for the dominant virulent strains of serogroup B meningococci in Norway is so low that we cannot be conclusive about the influence of vaccination on that strain in particular. Non-virulent meningococci and the vaccine strain have several outer membrane antigens (eg, H8, 5C, iron binding proteins, lipopolysaccharide) and epitopes in common. It does not seem likely that lack of significant effect of vaccination on carriage of non-virulent strains should be compatible with a pronounced effect on the dominant virulent strain. 24 cases of proven serogroup B systemic meningococcal disease occurred among non-volunteers. The risk of developing disease was not significantly higher among non-volunteers than in the placebo group. 16 cases occurred in non-volunteers in vaccinated schools, and 8 in placebo schools. The carriage rate for the dominant virulent strain in the Norwegian population is less than 0-5%, although higher in the 15-18 age group. Carriage before age 13 is rare.3 The most likely explanation for the higher occurrence of disease in "vaccine schools" is that the risk of infection was higher by chance. The
observation conflicts with the suggestion that the vaccine should afford substantial herd immunity. Our results indicate that the risk of invasive meningococcal B disease was the same in the placebo group as among non-volunteering students in secondary schools. If we calculate efficacy comparing vaccinees and non-volunteers in the same schools, the point estimate is 71 %. Our calculated vaccine efficacy reflects direct protection. Carriage of non-virulent meningococci induces bactericidal antibodies,4 thus contributing substantially to natural immunity in adults, and will possibly boost immunological memory to previous vaccination. If the vaccine protects against carriage of non-virulent meningococci, unvaccinated individuals in a largely vaccinated population might run a greater risk of not being immunised by non-virulent bacteria. Our participants are now being followed up openly. Having left school, they are for practical purposes randomised as individuals. Vaccine Department, National Institute of Public Health, N-0462 Oslo 4, Norway
GUNNAR BJUNE
1. Fme PEM. Meningococcal vaccine trial in Norway. Lancet 1990; 338: 1456-57. 2. Bjune G, Høiby EA, Grønnesby JK, et al. Effect of outer membrane vesicle vaccine
3.
4.
against group B meningococcal disease in Norway. Lancet 1991; 338: 1093-96. Caugant DA, Høiby EA, Scheel O, et al. Carnage of Neisseria meningitidis in a randomised sample of the Norwegian population. 5th European congress of clinical microbiology and infectious diseases, Sept, 1991, Oslo: abstr 1155. Caugant DA, Høiby EA, Rosenqvist E, Frøholm LO, Selander RK. Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol Infect (in press).
Pathogenesis of Crohn’s disease SiR,—Crohn’s disease may be a primary vasculitic process. To which types of vessels are involved we have relation of granulomas with blood and lymphatic vessels and have sought fibrinoid necrosis and inflammatory cell infiltration of the vessel wall. In 10 patients with active Crohn’s disease (3 female, aged 18-67,6 6 small bowel and 4 large bowel) we examined paraffm sections stained with haematoxylin/eosin, with Martius scarlet blue for fibrin, and with immunoperoxidase for vascular endothelium (QBendlO and UEA lectin) and macrophages (KPl). Granulomas seen with haematoxylin/ eosin were examined in serial sections to assess the nature of involved vessels and the presence of vasculitis. Out of 149 granulomas from all 10 patients, most were shown by ’ UEA to be closely associated with small channels lined by endothelium. The immunocytochemical and morphological characteristics suggested that these were lymphatics rather than blood vessels (figure). Impingement of granulomas on neighbouring vessel walls involved veins, not arteries, and was uncommon. In none of the vessel walls was there fibrinoid necrosis or other evidence of vasculitis.
study precisely investigated the
Section of ileum showing subserosal tortuous channels.
granulomas within
UEA lectin shows endothelium lining channels with interrupted and weak staining, suggestive of lymphatics, by contrast with strong endothelial staining of surrounding smaller and more regular blood vascular channels.
consumption of more fruits, vegetables, and grains, but fewer high-fat meat and dairy foods.6 By USA standards (163-5 g fat daily and 115-6 kg alcohol per year in 1986-881), the French food supply is quite healthy, but it is changing rapidly and for the worse. If current trends continue, one of the world’s most elegant and healthy cuisines-and the "French paradox"-will be lost forever. Neither gourmands nor cardiologists should remain complacent. Department of Nutrition, Food, and Hotel Management, New York University, New York, NY 10003 USA
MARION NESTLE
1. Food and
Agriculture Organisation. FAO food balance sheets, 1984-86 average. Rome: Food and Agriculture Organisation, 1991. 2. Putnam JJ, Allshouse JE. Food consumption, prices, and expenditures, 1968-89. Washington, DC: US Department of Agriculture, May, 1991. 3. US Department of Agriculture. Nutrient content of the USA food supply. HNIS Adm Rep No 299-21. Hyattsville, MD: US Department of Agriculture, August, 1988. 4. Spiller GA, ed. The Mediterranean diets in health and disease. New York: AVI/Van Nostrand Reinhold, 1991. 5. Aigrain P, Boulet D, Lambert JL, Laporte JP. La consommation du vin en France en 1990: evolution 1980-90—projections 1995-2000. Montpellier: Office National Interprofessionnel des Vins, Institut National de la Recherche Agronomique, September, 1991. 6. World Health Organisation. Diet, nutrition, and the prevention of chronic diseases. WHO Tech Rep Series 797. Geneva: World Health Organisation, 1990.
"Herd
immunity" and the meningococcal vaccine trial in Norway
SiR,—"Herd immunity" might explain! the result of our trial against serogroup B meningococcal disease in secondary schoolchildren which was randomised at school level Z If the vaccine protected the individual not only against invasive disease but also against carriage, the risk of infection in "vaccinated
protection
schools" would be less than in "placebo schools". Herd immunity will increase recorded efficacy if the randomised groups can be considered as largely separate populations with a high rate of internal meningococcal exchange. Consequently, the chance of revealing any efficacy will be reduced if individual randomisation is used. A 100% prevention of carriage would theoretically reduce the risk of infection for the non-volunteers proportionately to the percentage of vaccinees in the schools. At the start of the trial the incidence of meningococcal B disease in secondary schoolchildren in Norway was about 15/100 000; the total number of secondary school students was only 235 000. Even with a very high rate of volunteering and with a vaccine efficacy that did not decrease for five or six years, an individual-randomised experiment would have had slight chance of being conclusive. The efficacy calculated was the sum of direct and indirect protective efficacy, as Fine correctly pointed out.! The question is whether indirect protection with our vaccine is likely and if we have seen such an effect. In several phase II studies with pharyngeal swabs we found no evidence that vaccination significantly prevents acquisition of meningococcal carriage. Neither was the carriage terminated in a substantial number of those who were carriers at vaccination. These studies, however, do not exclude a more subtle effect on carriage. The frequency of carriage for the dominant virulent strains of serogroup B meningococci in Norway is so low that we cannot be conclusive about the influence of vaccination on that strain in particular. Non-virulent meningococci and the vaccine strain have several outer membrane antigens (eg, H8, 5C, iron binding proteins, lipopolysaccharide) and epitopes in common. It does not seem likely that lack of significant effect of vaccination on carriage of non-virulent strains should be compatible with a pronounced effect on the dominant virulent strain. 24 cases of proven serogroup B systemic meningococcal disease occurred among non-volunteers. The risk of developing disease was not significantly higher among non-volunteers than in the placebo group. 16 cases occurred in non-volunteers in vaccinated schools, and 8 in placebo schools. The carriage rate for the dominant virulent strain in the Norwegian population is less than 0-5%, although higher in the 15-18 age group. Carriage before age 13 is rare.3 The most likely explanation for the higher occurrence of disease in "vaccine schools" is that the risk of infection was higher by chance. The
observation conflicts with the suggestion that the vaccine should afford substantial herd immunity. Our results indicate that the risk of invasive meningococcal B disease was the same in the placebo group as among non-volunteering students in secondary schools. If we calculate efficacy comparing vaccinees and non-volunteers in the same schools, the point estimate is 71 %. Our calculated vaccine efficacy reflects direct protection. Carriage of non-virulent meningococci induces bactericidal antibodies,4 thus contributing substantially to natural immunity in adults, and will possibly boost immunological memory to previous vaccination. If the vaccine protects against carriage of non-virulent meningococci, unvaccinated individuals in a largely vaccinated population might run a greater risk of not being immunised by non-virulent bacteria. Our participants are now being followed up openly. Having left school, they are for practical purposes randomised as individuals. Vaccine Department, National Institute of Public Health, N-0462 Oslo 4, Norway
GUNNAR BJUNE
1. Fme PEM. Meningococcal vaccine trial in Norway. Lancet 1990; 338: 1456-57. 2. Bjune G, Høiby EA, Grønnesby JK, et al. Effect of outer membrane vesicle vaccine
3.
4.
against group B meningococcal disease in Norway. Lancet 1991; 338: 1093-96. Caugant DA, Høiby EA, Scheel O, et al. Carnage of Neisseria meningitidis in a randomised sample of the Norwegian population. 5th European congress of clinical microbiology and infectious diseases, Sept, 1991, Oslo: abstr 1155. Caugant DA, Høiby EA, Rosenqvist E, Frøholm LO, Selander RK. Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol Infect (in press).
Pathogenesis of Crohn’s disease SiR,—Crohn’s disease may be a primary vasculitic process. To which types of vessels are involved we have relation of granulomas with blood and lymphatic vessels and have sought fibrinoid necrosis and inflammatory cell infiltration of the vessel wall. In 10 patients with active Crohn’s disease (3 female, aged 18-67,6 6 small bowel and 4 large bowel) we examined paraffm sections stained with haematoxylin/eosin, with Martius scarlet blue for fibrin, and with immunoperoxidase for vascular endothelium (QBendlO and UEA lectin) and macrophages (KPl). Granulomas seen with haematoxylin/ eosin were examined in serial sections to assess the nature of involved vessels and the presence of vasculitis. Out of 149 granulomas from all 10 patients, most were shown by ’ UEA to be closely associated with small channels lined by endothelium. The immunocytochemical and morphological characteristics suggested that these were lymphatics rather than blood vessels (figure). Impingement of granulomas on neighbouring vessel walls involved veins, not arteries, and was uncommon. In none of the vessel walls was there fibrinoid necrosis or other evidence of vasculitis.
study precisely investigated the
Section of ileum showing subserosal tortuous channels.
granulomas within
UEA lectin shows endothelium lining channels with interrupted and weak staining, suggestive of lymphatics, by contrast with strong endothelial staining of surrounding smaller and more regular blood vascular channels.
