Attitudes and knowledge among parents or guardians of 12-year-old girls about HPV vaccination - A population-based survey in Iceland.

PURPOSE: To assess attitude and knowledge among parents or guardians of 12-year-old girls about human papillomavirus (HPV), cervical cancer, and HPV vaccination. Material andMethods: A mail survey was sent to a randomized sample of 1,000 parents or guardians of 12-year-old girls from a cohort of total 2,092 girls born in 1995 and registered in the Icelandic National Register by the end of December 2007. RESULTS: Of the 994 eligible parents, 583 (59%) returned the questionnaire. Majority of the respondents were mothers who had two or three children. More than one-third of respondents had university education and 84% were married or living with a partner. Over two-thirds did not know that HPV causes cervical cancer and genital warts. Almost all (> 90%) would vaccinate theirs daughters with a HPV vaccine, 73% said they would vaccinate their sons, or themselves if the vaccine was effective for them. Only 11% believed HPV vaccination would increase promiscuity or decrease cervical screening attendance. CONCLUSION: In Iceland, willingness to vaccinate young girls with HPV vaccine is high, however, knowledge about HPV infections is limited.

Age-specific measles mortality during the late 19th-early 20th centuries.

Measles mortality fell prior to the introduction of vaccines or antibiotics. By examining historical mortality reports we sought to determine how much measles mortality was due to epidemiological factors such as isolation from major population centres or increased age at time of infection. Age-specific records were available from Aberdeen; Scotland; New Zealand and the states of Australia at the end of the 19th and beginning of the 20th centuries. Despite the relative isolation of Australia, measles mortality was concentrated in very young children similar to Aberdeen. In the more isolated states of Tasmania, Western Australia and Queensland adults made up 14-15% of measles deaths as opposed to 8-9% in Victoria, South Australia and New South Wales. Mortality in Iceland and Faroe Islands during the 1846 measles epidemic was used as an example of islands isolated from respiratory pathogens. The transition from crisis mortality across all ages to deaths concentrated in young children occurred prior to the earliest age-specific mortality data collected. Factors in addition to adult age of infection and epidemiological isolation such as nutritional status and viral virulence may have contributed to measles mortality outcomes a century ago.

Enteropathogens in acute diarrhea: a general practice-based study in a Nordic country.

The epidemiology of infectious diarrhea influences the microbiological investigation of the disease, and is best elucidated through prospective studies. We undertook such a study in a Nordic country. Patients of all age groups who had acute diarrhea were recruited prospectively from general practice clinics in Iceland. They completed a questionnaire and provided stool samples for the detection of pathogenic viruses, bacteria, and parasites. Of the 464 recruited patients, 211 (45%) had 224 infections. The most common pathogens were calici- and rotaviruses (23% and 18% of 224 infections, respectively), Campylobacter jejuni (17%), Cryptosporidium species (12%), and Salmonella serotypes (10%). Other agents found were Giardia lamblia, astro- and adenoviruses, and Yersinia enterocolitica. Viral pathogens were associated with vomiting, illness for ≤7 days, and younger age groups, while bacterial pathogens were associated with fever, rectal pain, and local or foreign travel, and parasitic pathogens with illness for >7 days. Detection rates for viral infections in the elderly and for Cryptosporidium species were higher than expected. Our study indicates the existence of regional differences in pathogen prevalence that should be taken into account when implementing guidelines for stool testing in patients with acute diarrheal disease.

A national epidemic of campylobacteriosis in Iceland, lessons learned.

Epidemics often result in organizational, policy and technical changes within a country. In 1999, an epidemic of campylobacteriosis was reported in Iceland. The recent availability of fresh poultry products in the marketplace was suggested as the source of infection. This paper reports on the context of the epidemic, reviews interventions implemented to prevent campylobacteriosis, and discusses lessons learned. A retrospective study of interventions implemented in Iceland from June 1995 to December 2007 was conducted by interviewing key informants and reviewing Iceland's literature. Cumulative incidence rates of domestic campylobacteriosis by year and average incidence rates per epidemic period were calculated. Interventions included on-farm surveillance of Campylobacter, producer education, enhanced biosecurity measures, changes in poultry processing, a leak-proof packaging policy, a freezing policy for products from Campylobacter-positive poultry flocks, consumer education, and the creation of a legislated inter-organizational response committee. These interventions appear to have collectively contributed to a decrease in campylobacteriosis' incidence rate near pre-epidemic baseline levels. Expert consultations revealed that the implementation of a Campylobacter surveillance program in poultry and the freezing policy were critical to controlling the disease in the Icelandic population. It was also recognized that new multidisciplinary collaborations among public health, veterinary, and food safety authorities and a sustained co-operation from the poultry industry were integral factors to the mitigation of the epidemic. Iceland's response to the campylobacteriosis epidemic is a lesson learned of inter-disciplinary and inter-organizational precautionary public health action in the face of a complex public health issue.

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.

An international outbreak of Shiga toxin-producing Escherichia coli O157 infection due to lettuce, September-October 2007.

Between 14 September and 20 October 2007, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157 simultaneously occurred in the Netherlands and Iceland. A total of 50 laboratory-confirmed cases were reported with a STEC O157 infection caused by the same clone. The strain was of type O157:H-, PT8, positive for stx1, stx2, eae and e-hly, and sorbitol negative. The most probable cause of this international outbreak was contaminated lettuce, shredded and pre-packed in a Dutch food processing plant. Samples of the environment, raw produce and end products, taken at several vegetable growers and processing plants all tested negative for STEC O157. However, the only epidemiological link between the cases in the Netherlands and in Iceland was the implicated Dutch processing plant. In Europe, food products are often widely distributed posing the risk of potential spread of food borne pathogens simultaneously to several countries. This international outbreak emphasises the importance of common alert and surveillance systems in earlier detection of international outbreaks and better assessment of their spread.

A European outbreak of Salmonella enterica serotype Typhimurium definitive phage type 204b in 2000.

OBJECTIVE: To describe the clinical, epidemiologic and microbiological features of a large outbreak of infection with a multiresistant Salmonella enterica serotype Typhimurium definitive type DT204b infection involving at least 392 people in five European countries. METHODS: Icelandic public-health doctors responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). An international alert was sent out through Enter-net. All strains from England & Wales, The Netherlands, Scotland and Germany, and 17 of the outbreak isolates from Iceland, were phage-typed, screened for antimicrobial resistance, and subjected to molecular typing. Hypothesis-generating interviews were conducted, followed by case-control studies performed in Iceland and England. RESULTS: Isolates from cases in Iceland, England and Wales, The Netherlands, Scotland and Germany were identified as Typhimurium DT204b. The antimicrobial resistance pattern was ACGNeKSSuTTmNxCpL. All strains tested displayed an identical plasmid profile. Strains from five cases in England & Wales and five cases in Iceland possessed identical pulsed-field profiles. Although a common source was suspected, only Iceland implicated imported lettuce as a vehicle, with an analytic epidemiologic study (OR = 40.8; P = 0.005; 95% CI 2.7-3175). CONCLUSION: The identification of international outbreaks, necessary for investigation and control, can be facilitated by standardized phage-typing techniques, the electronic transfer of molecular typing patterns, formal and informal links established through international surveillance networks, and the early reporting of national outbreaks to such networks.

Campylobacter spp. in Icelandic poultry operations and human disease.

We describe the observed relationship of campylobacter in poultry operations to human cases in a closed environment. During 1999 in Iceland, domestic cases of campylobacteriosis reached peak levels at 116/100,000 and in 2000 dropped to 33/100,000. Approximately 62% of broiler carcass rinses were contaminated with Campylobacter spp. in 1999. During 2000, only 15% of the broiler flocks tested Campylobacter spp. positive. In 2000, carcasses from flocks which tested positive on the farms at 4 weeks of age were subsequently frozen prior to distribution. We suggest that public education, enhanced on-farm biological security measures, carcass freezing and other unidentified factors, such as variations in weather, contributed to the large reduction in poultry-borne campylobacteriosis. There is no immediate basis for assigning credit to any specific intervention. We continue to seek additional information to understand the decline in campylobacteriosis and to create a risk assessment model for Campylobacter spp. transmission through this well defined system.

[Quality control of antimicrobial usage in Reykjavik Hospital in 1994 - 1998: economic impact.].

AIMS: To investigate the effect of guidelines and supervision of the prescription of antimicrobial agents at Reykjavik Hospital on the cost and the amount used of these agents. MATERIAL AND METHODS: The investigation was conducted from 1994 to 1997. Guidelines were issued for the prescription of antimicrobial agents in empirical treatment and for prophylactics in surgery. The availability of these agents was reduced and the physicians had to order these drugs by filling out a special application form. These forms were later on used for the supervision by a pharmacist and an infectious disease physician of the use of antmicrobial agents and to monitor any change in the prescription of the agents. If needed the supervisors gave advice to the clinicians responsible for the patients care. The supervision took place at eight of the wards of the hospital and started at different times during May 1995 to March 1996. RESULTS: The cost of the usage of antimicrobial agents was reduced after the introduction of the supervision. However, as time passed from the implementation of the supervision the cost tended to increase again. The greatest cost reduction was achieved at the departments of surgery or 8.5 million Icelandic crowns. At the departments of medicine the cost reduction was 2.3 million crowns. By correcting for the cost of supervisory staff the real cost decrease was approximately 6 million crowns. The total amount of prescribed antimicrobial agents measured by the Standardised Daily Dosage was reduced in all the concerned wards by 3-14%. CONCLUSIONS: The real cost decreases after the implementation of supervision of the prescription of antimicrobial agents was approximately six million Icelandic crowns during 1994 to 1997. Also, the proportion of antimicrobial agents in the total cost of drugs was reduced after the supervision started in spite of increasing mean cost per Standardised Daily Dosage increased at the departments during the study period. The goal of reducing the amount of antimicrobial agents prescribed was also achieved.

Multiple-conformation and protonation-state representation in 4D-QSAR: the neurokinin-1 receptor system.

Using a 4D-QSAR approach (software Quasar) allowing for multiple-conformation, orientation, and protonation-state ligand representation as well as for the simulation of local induced-fit phenomena, we have validated a family of receptor surrogates for the neurokinin-1 (NK-1) receptor system. The evolution was based on a population of 500 receptor models and simulated during 40 000 crossover steps, corresponding to 80 generations. It yielded a cross-validated r(2) of 0.887 for the 50 ligands of the training set (represented by a total of 218 conformers and protomers) and a predictive r(2) of 0.834 for the 15 ligands of the test set (70 conformers and protomers). A series of five "scramble tests" (with an average predictive r(2) of -0.438) demonstrates the sensitivity of the surrogate toward the biological data, for which it should establish a QSAR. On the basis of this model, the activities of 12 new compounds - four of which have been synthesized and tested in the meantime - are predicted. For most of the NK-1 antagonists, the genetic algorithm selected a single entity - out of the up to 12 conformers or protomers - to preferably bind to the receptor surrogate. Moreover, the evolution converged at an identical protonation scheme for all NK-1 antagonists. This indicates that 4D-QSAR techniques may, indeed, reduce the bias associated with the choice of the bioactive conformation as each ligand molecule can be represented by an ensemble of conformations, orientations, and protonation states.

Flexsim-X: a method for the detection of molecules with similar biological activity

We describe the development of the method Flexsim-X, which can be used to detect molecules with similar biological activity. This procedure is based on comparing virtual affinity fingerprints made up from docking scores of the molecules with respect to a reference set of binding sites. Using a test data set consisting of ligands from five different activity classes and randomly chosen compounds, the reference panel of binding sites was optimized in terms of size and composition. Systematic approaches as well as genetic algorithm based (GA) optimization procedures have been evaluated. Additionally, the effectiveness of the method is illustrated.

TT virus infections among blood donors in Iceland: prevalence, genotypes, and lack of relationship to serum ALT levels.

BACKGROUND: The TT virus (TTV) is a newly identified blood-borne virus. Its association with disease is still unknown, and screening of blood donors has not been implemented. Several genotypes of the TTV have been identified. STUDY DESIGN AND METHODS: Three hundred seventy healthy blood donors were randomly selected and tested for TTV by the PCR method. Sequencing of a part of the genome was performed to identify various genotypes of the virus. ALT levels were determined in both infected and uninfected individuals. RESULTS: The TT virus (TTV), was detected in the sera of 23 (6.2%) of 370 healthy Icelandic blood donors; this prevalence is lower than that reported in Japan but higher than that in Scotland. The virus was found in all groups over the age of 19. Sequencing and phylogenetic analysis of 202 bp from open reading frame 1 demonstrated genotypes 1b and 2b 2c and genotype 4 isolates, with the latter bearing 89-percent nucleotide homology with other genotype 4 sequences deposited at GenBank. One sample showed a mixed genotype 1b/2c infection. Serum ALT levels were within normal limits in all infected individuals. CONCLUSION: The TTV carrier state does not cause significant liver injury.

Synthesis of cyclic dipeptide templates, their incorporation into peptides and studies on their conformational and biological properties.

This study investigated the diastereoselective synthesis of three dipeptide templates 1, 2 and 3, which may be regarded as conformationally restricted analogs of H-Gly-Xaa-OH, in which Xaa constitutes an aromatic amino acid. Bond formation between alpha-C of Gly and the aromatic moiety was achieved by proton-catalyzed intramolecular electrophilic aromatic substitution. The absolute configuration of the dipeptide templates was determined by single-crystal X-ray crystallography or by nuclear Overhauser enhancement measurements. A protective group strategy was elaborated to allow their incorporation into peptide sequences by liquid phase as well as by solid-phase peptide synthesis. The templates were used to generate an enkephalin analog 15, a modified peptidic neurokinin antagonist 20 and two dermorphin derivatives (24 and 33). Molecular dynamic simulations with 15 and 20 revealed the preference for a turn-like motif for 15. The biological activity, as investigated by respective receptor binding and functional assays, was strongly diminished with all four derivatives, indicating that their receptor-relevant molecular geometries lie outside the examined conformational space.

Immunogenicity of two efficacious outer membrane protein-based serogroup B meningococcal vaccines among young adults in Iceland.

Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.

[Measurements of plasma HIV-1 RNA in Iceland.].

OBJECTIVE: First to measure plasma HIV-1 RNA in Icelandic HIV infected individuals and second to evaluate the initial effects of new combination regimens on viral load and CD4+ cell counts in HIV infected patients in Iceland. MATERIAL AND METHODS: The cohort studied consis notted of all HIV infected individuals we received samples from during the period September 1995 to November 1996. HIV-1 RNA and CD4+ cells were measured initially and subsequently every three to six months except when a change was made in the antiretroviral regimen, when samples were measured before the change, three to four weeks later and then every three to six months. The quantitative measurement of viral RNA was performed using the Amplicor HIV Monitor Test (Roche Diagnostic Sys nottems). CD4+ cell counts were measured by flow cytometry. RESULTS: A total of 44 patients were evaluated. The initial RNA ranged from %lt; 2.6 logio to 6.13 logio with a mean of 5.02 log. CD4+ cell counts ranged from 2 to 641 per mm3 (mean 230 cells/mm3). Eleven patients had never been treated with antiretroviral drugs and had greater than 10 000 viral copies per mL of plasma. Twenty five of the patients were evaluated following a change in or initiation of a new treatment. The initial change in treatment led to a +0.7 to -2.88 log change in plasma RNA (mean -0.9 log) and a mean of 6.9 cells per mm3 increase in CD4+ cells. Saquinavir was added to two reverse transcriptase (RT) inhibitors in 11 patients with a resulting mean of 0.23 log fall in RNA levels (range +0.70 log to -0.78 log). Saquinavir plus one RT inhibitor were added to one RT inhibitor in six patients with a subsequent mean of 0.65 log reduction in viral load (range +0.24 to -2.26 log). Saquinavir plus two RT inhibitors were given to four antiretroviral naive patients with a resulting mean of 2.37 log reduction in viral load (range -1.8 log to -2.67 log). CONCLUSIONS: 1. In a mixed cohort of RT inhibitor naive and treated patients, the viral RNA ranged throughout the range of the RNA assay. 2. Changes in viral load following changes in treatment were quite variable. 3. Saquinavir alone added to two RT inhibitors did not lead to a significant reduction in viral load. 4. In antiretroviral naive patients the viral load was reduced 100 fold following treatment with saquinavir and two RT inhibitors.