Surveillance of influenza in Iceland during the 2009 pandemic.

In a pandemic setting, surveillance is essential to monitor the spread of the disease and assess its impact. Appropriate mitigation and healthcare preparedness strategies depend on fast and accurate epidemic surveillance data. During the 2009 influenza A(H1N1) pandemic, rapid improvements in influenza surveillance were made in Iceland. Here, we describe the improvements made in influenza surveillance during the pandemic , which could also be of great value in outbreaks caused by other pathogens. Following the raised level of pandemic influenza alert in April 2009, influenza surveillance was intensified. A comprehensive automatic surveillance system for influenza-like illness was developed, surveillance of influenza-related deaths was established and laboratory surveillance for influenza was strengthened. School absenteeism reports were also collected and compared with results from the automatic surveillance system. The first case of 2009 pandemic influenza A(H1N1) was diagnosed in Iceland in May 2009, but sustained community transmission was not confirmed until mid-August. The pandemic virus circulated during the summer and early autumn before an abrupt increase in the number of cases was observed in October. There were large outbreaks in elementary schools for children aged 6­15 years throughout the country that peaked in late October. School absenteeism reports from all elementary schools in Iceland gave a similar epidemiological curve as that from data from the healthcare system. Estimates of the proportion of the population infected with the pandemic virus ranged from 10% to 22%. This study shows how the sudden need for improved surveillance in the pandemic led to rapid improvements in data collection in Iceland. This reporting system will be improved upon and expanded to include other notifiable diseases, to ensure accurate and timely collection of epidemiological data.

The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor.

Fish oil is believed to alter the immune response and improve survival after infections in experimental animals. This effect may be due to altered production of the leukotrienes (LT). We, therefore, performed a study in order to evaluate whether the effect of fish oil on the immune response of experimental animals is mediated through altered production of the LT. Female NMRI mice in four groups were fed with fish oil, fish oil with 5-lipoxygenase (5-LO) inhibitor (Zileuton, Abbott Laboratories, Chicago, IL, USA), corn oil or corn oil with 5-LO inhibitor. After 6 weeks, the mice were infected with Klebsiella pneumoniae and the survival was monitored. The experiment was performed twice. Analysis was performed mainly on data pooled from both experiments. The survival of the groups fed with fish oil was increased, compared to that of all the other groups and when compared to the groups fed with fish oil with 5-LO inhibitor (log-rank test) the difference was significant (P = 0.007). It has been postulated that the effect of fish oil on the immune system is mediated through altered production of LT. In our study, blocking of the production of the LT eliminated the beneficial effects of fish oil. Our results are in concord with the hypothesis that the effect of fish oil is, at least partly, mediated through altered production of LT.

Development of immunoglobulin A in infancy and childhood.

Serum and salivary concentrations of immunoglobulin A1 (IgA1) and IgA2 were studied in 105 Icelandic children aged 0-12 years. Serum concentrations of both IgA1 and IgA2 increased slightly (P < 0.001) during childhood. The salivary IgA1/IgA2 ratio tended to decrease during the same period; this trend is less apparent when omitting the youngest children. The salivary IgA1 and IgA2 output could be high, even in children with low levels of serum IgA. Only polymeric IgA was found in whole saliva. Interestingly, in serum, most IgA1 and IgA2 were polymeric during infancy. The proportion of polymeric IgA decreased, when the concentration of IgA increased. The polymeric form of IgA might provide the infant with better protection against invading microorganisms by activation of the innate immune mechanisms.

[Trends in overweight and obesity in 45-64 year old men and women in Reykjavik 1975-1994.].

OBJECTIVE: The aim of this study was to assess possible changes in the prevalence of overweight and obesity in Iceland during the last decades. Furthermore, the possible effect of dietary changes on the observed trend in obesity prevalence was evaluated. MATERIAL AND METHODS: Participants came from stages III-V in the Reykjavik Health Study and the Reykjavik part of the MONICA studies from the period 1975-1994. The age groups 45-54 years and 55-64 years were examined. Only the information from the first visit of each person was included. The body mass index (BMI) for the participants was calculated and the percentage of those subjects considered overweight and obese according to WHO standards evaluated, using 25BMI<30 kg/m(2) as the cut-off point for overweight and BMI30 kg/m(2) as the cut-off point for obesity. Also, the observed trend in obesity prevalence is compared to changes in diet that have occurred in the same period. RESULTS: The results show that the mean weight and height of both men and women have been increasing during the study period. However, weight has increased more than can be accounted for by increased height, resulting in increased BMI. At the same time, the prevalence of overweight and obesity have increased, the relative increase in obesity far exceeding the relative increase in overweight. The prevalence of obesity more than doubled in both age groups of women during the study period, according to trend analyses. At the end of the period, almost 15% (95% confidence interval (CI), 9-22%) in the younger group of women and 25% (95% CI, 17-34%) in the older group were classified as obese. In the younger group of men, the prevalence of obesity almost doubled, while the observed increase in the older group was not statistically significant, according to trend analyses. The prevalence of obesity in the final period was about 19% (95% CI, 13-27%) and 17% (95% CI, 11-25%) in the younger and older groups of men, respectively. According to the food supply statistics there have been insignificant changes in the consumption of energy nutrients during the period. CONCLUSIONS: Overweight and obesity are becoming more common among middle-aged men and women in Reykjavik, during the period 1975-1994 and the rate of increase being comparable to that observed in many Western countries. It is urgent to respond to this problem by promoting a healthier lifestyle, both with respect to diet and physical activity.

[Homocysteine, folate and cobalamin in Icelandic men and women.].

OBJECTIVE: To determine reference intervals and interquartile ranges for total homocysteine (Hcy) folate and cobalamin in Icelandic men and women and to evaluate the correlation of Hcy to serum levels of the vitamins folate and cobalamin. MATERIAL AND METHODS: Blood samples were collected from 449 individuals over a period of three months, 291 men (mean age 48.3 years) and 158 women (mean age 49.8 years). Plasma Hcy was measured by a HPLC method with fluorescence detection; folate and cobalamin levels in serum were measured by an electroimmunochemical method on an ELECSYS system from Roche. RESULTS: The reference interval for Hcy, between 2.5% and 97.5% fractiles, estimated by parametric statistics, are 6.2-17.5 micromol/L for men and 4.8-14.1 micromol/L for women. Similarly the 95% reference intervals for folate and cobalamin were estimated using parametric statistics. A significant negative correlation was found between concentrations of folate and Hcy for both men and women (p<0.01) with a correlation coefficient of -0.39 and also between cobalamin and Hcy where the correlation coefficient is -0.20. CONCLUSIONS: Reference interval for Hcy from the general presumed healthy population is estimated here for the first time in Icelandic men and women and will be of value in cardiovascular risk assessments. The negative correlation between Hcy and folate and also Hcy and cobalamin, is in agreement with results from other studies and suggests that an improved vitamin status might be beneficial in lowering Hcy in a section of the population as has been suggested in numerous studies in other countries.

Serum immunoglobulinD in infants and children.

Serum immunoglobulinD (IgD) concentration is usually low in healthy individuals as compared to other immunoglobulin classes. Most studies on serum IgD are concerned with serum levels in healthy adults but reference values for young children and infants are not easily available. In order to establish age specific reference values we measured IgD levels in serum of 184 healthy Icelandic children, age 0-14 years and 60 healthy blood donors age 18-63, using the ELISA technique. Special attention was paid to the youngest age groups. Results showed low IgD values in infants and young children, gradually increasing until the age of 10 but then decreasing with age. We conclude that IgD gradually increases with age in childhood as other immunoglobulin classes but later declines. These findings can be of importance in revealing the function of IgD in the immune system as well as in the diagnosis of the hyper-IgD syndrome.

P.A. Schleisner: a pioneer in epidemiology.

In 1847 Schleisner (b. 1818) was sent from Copenhagen to the Vestmanna Islands in Iceland to study the epidemic of tetanus neonatorum. The neonatal mortality in those islands at that time was 600-740 per 1000 children. He built a small hospital and introduced treatment with Peru balsam of the umbilicus. Schleisner probably assumed that the infection was caused by airborne infection, contact infection or poor hygiene. The neonatal mortality fell to about 50 per 1000. Schleisner published his results in 1849. Semmelweiss published his observations in 1850 and Snow successfully fought the cholera epidemic in London in 1854. Schleisner deserves recognition as a pioneer in the field of epidemiology.

The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on citric acid cycle intermediates.

The modified nucleoside 2-methylthio-N-6-isopentenyl adenosine (ms2i6A) is present in position 37 (adjacent to and 3' of the anticodon) of tRNAs that read codons beginning with U except tRNA(i.v. Ser) in Escherichia coli. In Salmonella typhimurium, 2-methylthio-N-6-(cis-hydroxy)isopentenyl adenosine (ms2io6A; also referred to as 2-methylthio cis-ribozeatin) is found in tRNA, most likely in the species that have ms2i6A in E. coli. Mutants (miaE) of S. typhimurium in which ms2i6A hydroxylation is blocked are unable to grow aerobically on the dicarboxylic acids of the citric acid cycle. Such mutants have normal uptake of dicarboxylic acids and functional enzymes of the citric acid cycle and the aerobic respiratory chain. The ability of S. typhimurium to grow on succinate, fumarate, and malate is dependent on the state of modification in position 37 of those tRNAs normally having ms2io6A37 and is not due to a second cellular function of tRNA (ms2io6A37)hydroxylase, the miaE gene product. We suggest that S. typhimurium senses the hydroxylation status of the isopentenyl group of the tRNA and will grow on succinate, fumarate, or malate only if the isopentenyl group is hydroxylated.

Influenza vaccination in 22 developed countries: an update to 1995.

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.

Users of antiasthma drugs in Iceland: a drug utilization study.

There has been an increasing consensus worldwide on how to treat asthma, and, simultaneously, an increase in the sales of antiasthma drugs. However, little is known about actual drug use, dosage, combinations of drugs, etc., or about the clinical characteristics of patients using these drugs. All individuals with prescriptions for antiasthma drugs, who came to Icelandic pharmacies during March 1994, were invited to participate. By means of questionnaires, the pharmacists recorded the age and gender of the patient, the specialty of the prescribing doctor, as well as the name of the drug, total amount prescribed, and dosage. The patients were asked to answer another questionnaire on their clinical diagnosis, usage of other antiasthma drugs, etc. The pharmacists registered 2,026 individuals, with 2,687 prescriptions: 1,574 for beta2-agonists, 838 for inhaled corticosteroids, 208 for theophylline, 48 for anticholinergic drugs, and 19 for cromoglycates. One thousand, three hundred and fifty one patients answered the questionnaires. The majority (67%) claimed to have asthma, 18% chronic bronchitis, 11% emphysema and 5% other diseases or symptoms. Among those aged > or = 16 yrs with asthma, 93% used beta2-agonists, 62% inhaled corticosteroids, 19% theophylline, and very few used other drugs. The most commonly used combination (57%) was beta2-agonists with inhaled corticosteroids. Thirty one per cent used beta2-agonists as monotherapy, and 5% used only inhaled corticosteroids. Theophylline was used mainly in combination with beta2-agonists and inhaled corticosteroids. In conclusion, our data suggest that two thirds of antiasthma drug users have asthma and that most are treated according to present guidelines. The use of inhaled corticosteroids, however, seems somewhat less than optimal.

What is the long term value of multiphasic health screening and the initial judgement of benefit?

The long term effects of multiphasic health screening (MHS) are rarely studied. In 1964 a random sample of 546 women and 544 men born 1899, 1904, 1909, 1914 or 1919 equally distributed on cohorts from the Swedish town Eskilstuna were invited to examination. For several reasons 167 persons (15%) did not participate in the study. In 1969 the whole sample was invited to a second MHS together with a control group that had not been exposed to MHS. Furthermore, 79 of those alive 1989 born 1899 or 1904 and examined 1964 and 1969 were reexamined. Over all survival rate 1989 for those examined 1964 was for males 18% and for females 35%. Screening instruments 1964 and 1969 were questionnaires, laboratory tests, antropometric measurements, ECG, measurement of blood pressure, chest radiography, peak expiratory flow (PEF), tonometry and fundoscopy of the eyes, audiometric screening, dental, gynecological and general clinical examination. Systolic hypertension for both sexes, low PEF and smoking, low cholesterol in women were negatively related to survival. Of 18 diabetics only one was alive at follow-up. No association was found between BMI and mortality for men, but some (1964 p < 0.01; 1969 p < 0.05) for women. Altogether 87 individuals were 1969 judged to have had some benefit of the MHS in 1964, 40 of them substantial. This was, however, not statistically significantly associated with improved survival. Of the reexamined survivors 86% reported to be generally satisfied with their life situation. The prognostic value of graded benefit was analysed in some detail. The survival to age 85 in the group allotted any benefit was somewhat less good (37%) than in the group with no benefit (44%). The difference did not reach statistical significance.

Mutation in the structural gene for release factor 1 (RF-1) of Salmonella typhimurium inhibits cell division.

A temperature-sensitive mutant of Salmonella typhimurium LT2 was isolated. At the nonpermissive temperature cell division stopped and multinucleated filaments were formed. DNA, RNA, or protein synthesis was not affected until after about two generations. Different physiological conditions, such as anaerobiosis and different growth media, suppress the division deficiency at high temperatures. Certain mutations causing a reduced polypeptide chain elongation rate also suppress the division deficiency. The mutation is recessive and shown to be in the structural gene for release factor I (prfA). DNA sequencing of both the wild-type (prfA+) and mutant (prfA101) allele revealed a GC-to-AT transition in codon 168. Like other known prfA mutants, prfA101 can suppress amber mutations. The division defect in the prfA101 mutant strain could not be suppressed by overexpression of the ftsQAZ operon. Moreover, at the nonpermissive temperature the mutant shows a normal heat shock and SOS response and has a normal ppGpp level. We conclude that the prfA101-mediated defect in cell division is not directed through any of these metabolic pathways, which are all known to affect cell division. We speculate that the altered release factor I induces aberrant synthesis of an unidentified protein(s) involved in the elaborate process of septation.

[Incidence and prevalence of positive tuberculin skin test reactions among schoolchildren.].

OBJECTIVES: To investigate the incidence and prevalence of positive tuberculin skin test reactions in schoolchildren from six to 16 years of age. MATERIAL AND METHODS: Data from tuberculin test school surveys in Reykjavik during the years 1958 to 1991 are available for almost all individuals of each age cohort. During 1958 to 1991 schoolchildren from six to 16 years of age were tested annually. In Iceland regular BCG vaccination in children or aldults has never been applied. RESULTS: Incidence of positive tests in all ages fell from 2.5 (per 1000 tested per year) from 1958 down to 0.5 in the mid seventies and after that the incidence remained low. Prevalence of positive tests for the same age group in different age cohorts showed that for each age group from seven to 16 years positive tests were most common at the beginning of the study period but decreased successively to the beginning of the seventies. The prevalence of positive tests was low and almost unchanged during 1976 to 1991 and varied from 0 -1.6 (per 1000 tested per year) among children seven to eight years of age, 0-2.9 among children 11 to 12 years of age and from 0-3.8 among those aged 15 to 16 years. CONCLUSION: During the last decade little has been gained by systematic testing for tuberculosis as a tool for finding newly infected persons or carriers of M. Tuberculosis. It seems to us that the results of this study do not justify systematic testing for tuberculous infection in all schoolchildren. Increased emphasis should be placed on testing among risk groups such as immigrants from countries where tuberculosis is endemic. Recent infection due to M. Tuberculosis is a high risk factor for tuberculosis. Search for newly infected persons in close contact with infectious patients with tuberculosis should have priority next to the diagnosis and treatment of the patients. Tests for tuberculosis among those who want to immigrate to Iceland circumscribe another risk group where containment of tuberculosis is possible.

[Antiasthmatic drugs in Iceland - an epidemiological survey.].

The use of antiasthmatic drugs in Iceland has increased considerably during the last 15 years. The aim of this study was to assess in a well-defined epidemiological population the characteristics of those using antiasthmatic drugs; age, gender, speciality of prescribing doctor, dosage and combinations of drugs. Also their clinical diagnosis and symptoms. All individuals with prescriptions for antiasthmatic drugs that came to Icelandic pharmacies during March 1994 were invited to participate. Altogether 2026 individuals accepted (2687 prescriptions). There were proportionally more young males and middle aged females (p<0.0001). The prescriptions for beta2-adrenergic drugs were 1574, 838 for inhaled corticosteroids, 208 for theofylline, 49 for anticholinergic drugs and 19 for natrium chromoglycate. General practitioners had prescribed 68% of the drugs, 16.3% were from pulmonary physicians and/or allergists, 6.4% from pediatricians and 9.3% from other doctors. The treatment had been started by specialists other than general practitioners in more than 60% of cases. Among those using inhaled drugs 95% had been tought how to do so. The majority (66.9%) claimed that they were using the drugs because of asthma, 17.8% because of chronic bronchitis, 10.7% because of emphysema and 4.6% for other reasons. There were altogether 591 individuals (2=16 years) with asthma who answered the questionnaire. Among them 93% used beta2-adrenergic drugs, 62% inhaled corticoseroids, 19% theofylline and very few used other drugs. The most commonly used combination (57%) was beta-adrenergic drugs and inhaled corticoseroids. Altogether 31% used beta2-adrenergic drugs as monotherapy and 5% had only inhaled corticosteroids. Theofylline is mainly used in combination with beta-adrenergic drugs and inhaled corticosteroids. Its use as monotherapy is infrequent (2%). Among those 209 asthma patients who had used oral corticosteroids the last 12 months, 73% were using some kind of inhaled corticosteroids and 27% not.

[Measurement of thyroid autoantibodies in Graves' disease.].

It is thought that dietary iodine may play a role in thyroid autoimmune reactivity. Iceland is an iodine rich area and therefore it seemed interesting to measure autoantibodies against TSH receptor (TRAb), thyroid peroxidase (TPO) and thyroglobulin (TG) in Icelandic patients with Graves' disease. Serum samples were collected from 47 patients with untreated Graves' disease, 73 patients with Graves' disease that had been treated with radioiodine (U1I), most of them (56) hypothyroid following the treatment and therefore on T4 replacement, others euthyroid. Measurements were also done on samples from a reference group of 74 healthy volunteers. All reference values are 0.95 fractile. Untreated patients with Graves' disease had TRAb values over reference range in 68.1% of cases being similar to what others have observed. The untreated patients with Graves' disease had TPO antibody measurement positive in 50.0% of cases and TG antibodies in 34.7%. This is much lower frequency of positive tests than observed elsewhere when measured with ELISA. Although methodological factors might play a role, this difference could also be explained by difference in iodine intake. The antibodies were less frequent in radioiodine treated patients than in the untreated ones. This is in agreement with the observation that serum levels of these antibodies tend to decrease with time from treatment. The antibody measurements did not differentiate between radioiodine treated patients with Graves' disease needing T4 replacement and those who did not.

Influenza vaccination in 18 developed countries, 1980-1992.

Influenza continues to be an important cause of preventable morbidity and mortality. Although influenza vaccine is widely recommended for older high-risk individuals, no studies have compared its use in different countries. We gathered information on influenza vaccine distribution in 18 developed countries for the period 1980-1992. During the 1980s there was a > or = 10-fold difference in annual per capita vaccine distribution among these countries, and in 1992 the difference was still more than 7-fold. Several countries demonstrated large increases in vaccine use over the study period, some showing substantial increases in specific years. Thirteen of the 18 countries recommend influenza vaccination for all elderly persons and 11 countries provide reimbursement for vaccination through national or social health insurance. These countries tend to have higher levels of vaccine use. Historical, economic and political factors also affect vaccination practices and policies, but their relationships to differences in vaccine use between countries are not known. A better understanding of why the use of influenza vaccine varies among countries will be important if its protective benefits are to be fully realized.

Synthesis and function of isopentenyl adenosine derivatives in tRNA.

Isopentenyl adenosine derivatives can be found next to the anticodon (position 37) in tRNA from both the Bacteria and Eucarya domains. These modified nucleosides improve the efficiency of tRNA in translation, can increase and decrease translational fidelity, and make the tRNA less codon context sensitive. In bacteria the synthesis of isopentenyl adenosine derivatives seems to be linked to iron metabolism and central metabolic pathways.