Search

Background: Limited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined., Methods: Unrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression., Results: Treatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35-56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32-5.41) after first treatment attempt., Conclusion: By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SO, MG, RHF, and VR report consultancy and speaker's fees from Gilead Sciences. MHel's institute receives funding from Gilead Sciences and AbbVie for investigator-initiated research on which MHel is a chief investigator. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Treatment as Prevention for Hepatitis C program started in 2016 in Iceland, offering treatment with direct-acting antivirals to hepatitis C virus (HCV)-infected individuals. Reinfections through injection drug use (IDU) can hamper elimination efforts. We determined reinfection rates of HCV among patients in the program., Methods: Clinical data were gathered prospectively. The study cohort consisted of HCV-cured patients with an estimated sustained virologic response between 1 February 2016 and 20 November 2018, with follow-up until 20 November 2019. The observation period and time until reinfection was estimated using a single random point imputation method coupled with Monte Carlo simulation. The reinfection rates were expressed as reinfections per 100 person-years (PY)., Results: In total, 640 treatments of 614 patients (417 male; mean age, 44.3 years) resulted in cure, with 52 reinfections subsequently confirmed in 50 patients (37 male). Follow-up was 672.1 PY, with a median time to reinfection of 232 days. History of IDU was reported by 523 patients (84.8%) and recent IDU with 220 treatments (34.4%). Stimulants were the preferred injected drug in 85.5% of patients with a history of IDU. The reinfection rate was 7.7/100 PY. Using multivariate Cox proportional hazards models for interval-censored data, age (hazard ratio, 0.96 [95% confidence interval, .94-.99]) and recent IDU (2.91 [1.48-5.76]) were significantly associated with reinfection risk., Conclusions: The reinfection rate is high in a setting of widespread stimulant use, particularly in young people with recent IDU. Regular follow-up is important among high-risk populations to diagnose reinfections early and reduce transmission., Clinical Trials Registration: NCT02647879., Competing Interests: Potential conflicts of interest. S. O. and M. G. report consultancy and speaker’s fees from Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed, (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Acute gastroenteritis poses a significant burden on young children, families, health care facilities and societies. Rotavirus is the most common pathogen, but rotavirus infections are vaccine preventable. Information on the epidemiology of gastroenteritis in Icelandic children has until now not been available and rotavirus vaccination is currently not offered to Icelandic infants. The objective of this study was to assess the burden of rotavirus acute gastroenteritis in young children in Iceland and determine the potential benefit of adding rotavirus vaccine to the Icelandic childhood immunization schedule., Methods: For a two-year period, children < 6 years old attending a children's emergency department for acute gastroenteritis were recruited at the Children's Hospital in Reykjavík, Iceland. Demographic information and Vesikari scores were registered. Stool samples were analyzed for pathogens. Duration of symptoms, treatment given, and secondary household infections were among the collected information. Annual cost of the infections in young children was estimated based on health care expenditures and lost days of parental work., Results: 325 children were included in the study, 75% of which were ≤ 24 months old. A pathogen was identified in 80% of cases, of which rotavirus was identified in 54%. Rotavirus caused a more severe disease than other pathogens, more often leading to fluid treatment in the emergency department and admissions. Median duration of rotavirus-illness was six days and caused a median of four days lost from work by parents. The estimated annual cost of rotavirus acute gastroenteritis was €2.9 million., Conclusions: Rotavirus causes significant disease burden in young children. Although rarely life-threatening in high income countries, the costs for society are substantial. The inclusion of rotavirus vaccine in the national immunization schedule will reduce the disease burden and would be cost-saving in Iceland., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: WHO has set targets to eliminate hepatitis C virus (HCV) infection as a global health threat by 2030 through a 65% reduction in HCV-related deaths and 80% reduction in HCV incidence. To achieve these goals, WHO set service coverage targets of 90% of the infected population being diagnosed and 80% of eligible patients being treated. In February, 2016, Iceland initiated a nationwide HCV elimination programme known as treatment as prevention for hepatitis C (TraP HepC), which aimed to maximise diagnosis and treatment access. This analysis reports on the HCV cascade of care in the first 3 years of the programme., Methods: This population-based study was done between Feb 10, 2016, and Feb 10, 2019. Participants aged 18 years or older with permanent residence in Iceland and PCR-confirmed HCV were offered direct-acting antiviral (DAA) therapy. The programme used a multidisciplinary team approach in which people who inject drugs were prioritised. Nationwide awareness campaigns, improved access to testing, and harm reduction services were scaled up simultaneously. The number of infected people in the national HCV registry was used in combination with multiple other data sources, including screening of low-risk groups and high-risk groups, to estimate the total number of HCV infections. The number of people diagnosed, linked to care, initiated on treatment, and cured were recorded during the study. This study is registered with ClinicalTrials.gov, NCT02647879., Findings: In February, 2016, at the onset of the programme, 760 (95% CI 690-851) individuals were estimated to have HCV infection, with 75 (95% CI 6-166) individuals undiagnosed. 682 individuals were confirmed to be HCV PCR positive. Over the next 3 years, 183 new infections (including 42 reinfections) were diagnosed, for a total of 865 infections in 823 individuals. It was estimated that more than 90% of all domestic HCV infections had been diagnosed as early as January, 2017. During the 3 years, 824 (95·3%) of diagnosed infections were linked to care, and treatment was initiated for 795 (96·5%) of infections linked to care. Cure was achieved for 717 (90·2%) of 795 infections., Interpretation: By using a multidisciplinary public health approach, involving tight integration with addiction treatment services, the core service coverage targets for 2030 set by WHO have been reached. These achievements position Iceland to be among the first nations to subsequently achieve the WHO goal of eliminating HCV as a public health threat., Funding: The Icelandic Government and Gilead Sciences., Competing Interests: Declaration of interests SO, MG, RHF, and VR report consultancy and speaker's fees from Gilead Sciences. MHel's institute receives funding from Gilead Sciences and AbbVie for investigator-initiated research on which MHEl is a chief investigator. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during a well characterized epidemic in Iceland. We demonstrate how the viral concentration decreased in those newly diagnosed as the epidemic transitioned from exponential growth phase to containment phase. The viral concentration in the cases identified in population screening decreased faster than in those symptomatic and considered at high risk and that were targeted by the healthcare system. The viral concentration persists in recovering individuals as we found that half of the cases are still positive after two weeks. We demonstrate that accumulation of mutations in SARS-CoV-2 genome can be exploited to track the rate of new viral generations throughout the different phases of the epidemic, where the accumulation of mutations decreases as the transmission rate decreases in the containment phase. Overall, the molecular signatures of SARS-CoV-2 infections contain valuable epidemiological information that can be used to assess the effectiveness of containment measures.

Picornaviruses (family Picornaviridae) are small, nonenveloped, positive-sense, single-stranded RNA viruses. The members of this family are currently classified into 47 genera and 110 species. Of picornaviruses, entero- and parechoviruses are associated with aseptic meningitis. They are transmitted via fecal-oral and respiratory routes, and occasionally, these viruses may cause a brief viremia and gain access to central nervous system (CNS). During the diagnostic screening of entero- and parechovirus types in Finland in year 2013-14, we detected a cluster of echovirus 4 (E4) infections in young adults and adolescents. As E4 is infrequently detected in Finland, we contacted several Northern and Central European laboratories that conduct routine surveillance for enteroviruses and, for those who have had E4 cases, we send a query for E4 sequences and data. Here we report CNS infections caused by E4 in Finland, Sweden, Norway, Denmark, Iceland and Germany in 2013 and 2014, and show that the E4 detected in these countries form a single lineage. In contrast, E4 strains circulating in these countries preceding the year 2013, and those circulating elsewhere in Europe during 2013-2014, formed several independent clusters., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population., Methods: We targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons. We sequenced SARS-CoV-2 from 643 samples., Results: As of April 4, a total of 1221 of 9199 persons (13.3%) who were recruited for targeted testing had positive results for infection with SARS-CoV-2. Of those tested in the general population, 87 (0.8%) in the open-invitation screening and 13 (0.6%) in the random-population screening tested positive for the virus. In total, 6% of the population was screened. Most persons in the targeted-testing group who received positive tests early in the study had recently traveled internationally, in contrast to those who tested positive later in the study. Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older. Fewer females than males received positive results both in targeted testing (11.0% vs. 16.7%) and in population screening (0.6% vs. 0.9%). The haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time. The percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening., Conclusions: In a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts. (Funded by deCODE Genetics-Amgen.)., (Copyright © 2020 Massachusetts Medical Society.)

IntroductionSequence-based typing of hepatitis A virus (HAV) is important for outbreak detection, investigation and surveillance. In 2013, sequencing was central to resolving a large European Union (EU)-wide outbreak related to frozen berries. However, as the sequenced HAV genome regions were only partly comparable between countries, results were not always conclusive.AimThe objective was to gather information on HAV surveillance and sequencing in EU/European Economic Area (EEA) countries to find ways to harmonise their procedures, for improvement of cross-border outbreak responses.MethodsIn 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on HAV surveillance practices in EU/EEA countries. The survey enquired whether a referral system for confirming primary diagnostics of hepatitis A existed as well as a central collection/storage of hepatitis A cases' samples for typing. Questions on HAV sequencing procedures were also asked. Based on the results, an expert consultation proposed harmonised procedures for cross-border outbreak response, in particular regarding sequencing. In 2016, a follow-up survey assessed uptake of suggested methods.ResultsOf 31 EU/EEA countries, 23 (2014) and 27 (2016) participated. Numbers of countries with central collection and storage of HAV positive samples and of those performing sequencing increased from 12 to 15 and 12 to 14 respectively in 2016, with all countries typing an overlapping fragment of 218 nt. However, variation existed in the sequenced genomic regions and their lengths.ConclusionsWhile HAV sequences in EU/EEA countries are comparable for surveillance, collaboration in sharing and comparing these can be further strengthened.

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879., (© 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Objective: Hepatitis E virus (HEV) infection has been reported to be more prevalent in the developed countries than previously thought. HEV infection is an important differential diagnosis in patients with drug-induced liver injury (DILI). The prevalence of hepatitis E was investigated in the general population of Iceland, among pig farmers and patients with DILI., Materials and Methods: Serum samples were tested for hepatitis E IgG, with two commercial ELISA tests: Diagnostic Bioprobes Srl. (Dia Pro) and the Wantai HEV IgG and subjects repeatedly reactive were tested with an immunoblot assay (RecomLINE). Three groups were tested: (1) healthy volunteers (HV), (2) pig farm workers (PFWs) and (3) patients participating in a nationwide prospective study on DILI., Results: Overall 291 individuals were tested, HV (n = 195), PFW (n = 21) and DILI (n = 75). Only 6/291 (2.1%) tested positive for IgG antibodies to HEV in all three tests. Three HV were HEV IgG antibody positive and three in the DILI group. One PFW tested positive in the Dia Pro and Wantai tests but not in the immunoblot assay. All but one of the positive individuals in all three tests was either of foreign national origin or had spent extended period of time outside of Iceland., Conclusions: The seroprevalence of hepatitis E appears to be lower in Iceland than majority of recent studies in other western countries have demonstrated. This may be due to relative isolation and severe restriction on import of livestock from other countries.

Background: The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies., Methods: Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality., Results: The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcus pneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10000), Mycoplasma pneumoniae < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of M pneumoniae ( P < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae ( P = .02). Symptoms and outcomes were similar irrespective of microbial etiology., Conclusions: Pneumococci, M pneumoniae , and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified.

Introduction: Hepatitis A virus (HAV) epidemics occurred repeatedly in Iceland in the early 20th century, but since then few cases have been reported and no epidemics since 1952. The latest Icelandic studies on HAV from around 1990 showed low incidence of infection and de-- creasing prevalence of antibodies. The objective of this study was to determine the incidence, clinical presentation and origin of HAV, abroad or in Iceland., Material and Methods: A retrospective search was undertaken on all patients with positive anti-HAV IgM during the 11 years period of 2006-2016 in the virological database of the National University Hospital of Iceland. Clinical data was collected from medical records on symptoms at diagnosis, blood test results and possible route of transmission., Results: A total of 12 individuals were diagnosed with acute hepatitis A during the period and 6691 HAV total andibody tests and 1984 HAV IgM antibody tests were performed. Nine (75%) had been abroad within 7 weeks from initial symptoms. The most common symptoms were jaundice (83%), fever (67%) and nausea and/or vomiting (58%). 50% were admitted to a hospital. 42% had elevated INR/PT. Everyone sur-vived without complications., Conclusion: Annually, approximately one case of acute hepatitis A was diagnosed in Iceland during the study period but a very high number of antibody tests were performed. The majority of cases occurred among individuals who had recently been abroad. If patients have jaundice, fever and nausea, testing for HAV infection should be undertaken. HAV is not endemic in Iceland.

Objective: To determine the frequency of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes., Methods: A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006-2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records., Result: Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain-Barré syndrome following the infection., Conclusion: A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.

Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches. Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996-2012, p=0.003). Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy. A bbreviations : ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers' exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann-Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol : polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance.

The molecular epidemiology of HIV-1 in Iceland has not been described so far. Detailed analyses of the dynamics of HIV-1 can give insights for prevention of virus spread. The objective of the current study was to characterize the genetic diversity and transmission dynamics of HIV-1 in Iceland. Partial HIV-1 pol (1020bp) sequences were generated from 230 Icelandic samples, representing 77% of all HIV-1 infected individuals reported in the country 1985-2012. Maximum likelihood phylogenies were reconstructed for subtype/CRF assignment and determination of transmission clusters. Timing and demographic growth patterns were determined in BEAST. HIV-1 infection in Iceland was dominated by subtype B (63%, n=145) followed by subtype C (10%, n=23), CRF01&#95;AE (10%, n=22), sub-subtype A1 (7%, n=15) and CRF02&#95;AG (7%, n=15). Trend analysis showed an increase in non-B subtypes/CRFs in Iceland over the study period (p=0.003). The highest proportion of phylogenetic clustering was found among injection drug users (IDUs; 89%), followed by heterosexuals (70%) and men who have sex with men (35%). The time to the most recent common ancestor of the oldest subtype B cluster dated back to 1978 (median estimate, 95% highest posterior density interval: 1974-1981) suggesting an early introduction of HIV-1 into Iceland. A previously reported increase in HIV-1 incidence among IDUs 2009-2011 was revealed to be due to two separate outbreaks. Our study showed that a variety of HIV-1 subtypes and CRFs were prevalent in Iceland 1985-2012, with subtype B being the dominant form both in terms of prevalence and domestic spread. The rapid increase of HIV-1 infections among IDUs following a major economic crisis in Iceland raises questions about casual associations between economic factors, drug use and public health., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden., (© 2015 John Wiley & Sons Ltd.)

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved., (© 2015 John Wiley & Sons Ltd.)

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995)., (© 2015 John Wiley & Sons Ltd.)

Herpes simplex encephalitis (HSE) is a serious disease with 10-20% mortality and high rate of neuropsychiatric sequelae. This study is a long-term, nationwide study in a single country, Iceland. Clinical data were obtained from patient records and from DNA PCR and antibody assays of CSF. Diagnosis of HSE was classified as definite, possible or rejected based on symptoms, as well as virological, laboratory and brain imaging criteria. A total of 30 definite cases of HSE were identified during the 25 year period 1987-2011 corresponding to incidence of 4.3 cases/106 inhabitants/year. Males were 57% of all patients, median age 50 years (range, 0-85). Fever (97%), cognitive deficits (79%), impaired consciousness (79% with GCS < 13), headache (55%) and seizures (55%) were the most common symptoms. Brain lesions were found in 24 patients (80%) by MRI or CT. All patients received intravenous acyclovir for a mean duration of 20 days. Three patients (10%) died within one year and 21/28 pts (75%) had a Karnofsky performance score of <70% with memory loss (59%), dysphasia (44%), frontal symptoms (44%) and seizures (30%) as the most frequent sequelae. Mean delay from onset of symptoms to treatment was 6 days; this was associated with adverse outcome. In conclusion, the incidence of `HSE is higher than recently reported in a national registry study from Sweden. Despite advances in rapid diagnosis and availability of treatment of HSE, approximately three of every four patients die or are left with serious neurological impairment.

Background: Iterative reconstruction (IR) algorithms improve image quality and allow for radiation dose reduction in CT. Dose reduction is particularly challenging in brain CT where good low-contrast resolution is essential. Ideally, evaluation of image quality combines objective measurements and subjective assessment of clinically relevant quality criteria. Subjective assessment is associated with various pitfalls and biases., Purpose: To evaluate the potential of the hybrid IR algorithm iDOSE(4) to preserve image quality in phantom and clinical brain CT acquired with 30% reduced radiation dose, and to discuss the image quality assessment methods., Material and Methods: Forty patients underwent two consecutive brain CTs with normal radiation dose (ND) and 30% reduced dose (RD). Both ND and RD were reconstructed with FBP. In addition the reduced dose CTs were reconstructed with two levels of IR (ID2, ID4). Three image quality criteria (grey-white-matter discrimination, basal ganglia delineation, general image quality) were graded and ranked by six neuroradiologists. Noise levels and contrast-to-noise ratios (CNR) were measured in clinical data. Noise, signal-to-noise ratio (SNR), spatial resolution, and noise-power spectrum (NPS) were also assessed in a phantom., Results: Subjective image quality was considered adequate for clinical use for all reconstructions, graded good or excellent in 93% of cases for ND, 83% for ID4, 79% for ID2, and 67% for RD. For all quality parameters, ID4 and ID2 were graded better than RD (P < 0.0055 and P < 0.035), but worse than ND (P < 0.001). In clinical images, objective measurements showed lower noise and significantly higher CNR in ID4 compared with ND and RD (P < 0.001). CNR was similar for ID2 and ND. In the phantom, IR reduced noise while maintaining spatial resolution and NPS., Conclusion: The IR algorithm improves image quality of reduced dose CTs and consistently delivers sufficient image quality for clinical purposes. Pitfalls related to subjective assessment can be addressed with careful study design.

Objective: The purpose of this study was to evaluate the potential of a hybrid iterative reconstruction algorithm for improving image quality in craniocervical CT angiography (CTA) and to assess observer performance., Subjects and Methods: Thirty patients (mean age, 58 years; range 16-80 years) underwent standard craniocervical CTA (volume CT dose index, 6.8 mGy, 2.8 mSv). Images were reconstructed using both filtered back projection (FBP) and a hybrid iterative reconstruction algorithm. Five neuroradiologists assessed general image quality and delineation of the vessel lumen in seven arterial segments using a 4-grade scale. Interobserver and intraobserver variability were determined. Mean attenuation and noise were measured and signal-to-noise and contrast-to-noise ratios calculated. Descriptive statistics are presented and data analyzed using linear mixed-effects models., Results: In pooled data, image quality in iterative reconstruction was graded superior to FBP regarding all five quality criteria (p < 0.0001), with the greatest improvement observed in the vertebral arteries. Iterative reconstruction resulted in elimination of arterial segments graded poor. Interobserver percentage agreement was significantly better (p = 0.024) for iterative reconstruction (69%) than for FBP (66%) but worse than intraobserver percentage agreement (mean, 79%). Noise levels, signal-to-noise ratio, and contrast-to-noise ratio were significantly (p < 0.001) improved in iterative reconstruction at all measured levels., Conclusion: The iterative reconstruction algorithm significantly improves image quality in craniocervical CT, especially at the thoracic inlet. Despite careful study design, considerable interobserver and intraobserver variability was noted.

Objective: To evaluate the image quality produced by six different iterative reconstruction (IR) algorithms in four CT systems in the setting of brain CT, using different radiation dose levels and iterative image optimisation levels., Methods: An image quality phantom, supplied with a bone mimicking annulus, was examined using four CT systems from different vendors and four radiation dose levels. Acquisitions were reconstructed using conventional filtered back-projection (FBP), three levels of statistical IR and, when available, a model-based IR algorithm. The evaluated image quality parameters were CT numbers, uniformity, noise, noise-power spectra, low-contrast resolution and spatial resolution., Results: Compared with FBP, noise reduction was achieved by all six IR algorithms at all radiation dose levels, with further improvement seen at higher IR levels. Noise-power spectra revealed changes in noise distribution relative to the FBP for most statistical IR algorithms, especially the two model-based IR algorithms. Compared with FBP, variable degrees of improvements were seen in both objective and subjective low-contrast resolutions for all IR algorithms. Spatial resolution was improved with both model-based IR algorithms and one of the statistical IR algorithms., Conclusion: The four statistical IR algorithms evaluated in the study all improved the general image quality compared with FBP, with improvement seen for most or all evaluated quality criteria. Further improvement was achieved with one of the model-based IR algorithms., Advances in Knowledge: The six evaluated IR algorithms all improve the image quality in brain CT but show different strengths and weaknesses.

The patient presented below gives us the opportunity to discuss challenges in the diagnosis of drug-induced liver injury in an era of increasing awareness of hepatitis E., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Computed tomography (CT) of the brain is performed with high local doses due to high demands on low contrast resolution. Advanced algorithms for noise reduction might be able to preserve critical image information when reducing radiation dose., Purpose: To evaluate the effect of advanced noise filtering on image quality in brain CT acquired with reduced radiation dose., Material and Methods: Thirty patients referred for non-enhanced CT of the brain were examined with two helical protocols: normal dose (ND, CTDI(vol) 57 mGy) and low dose (LD, CTDI(vol) 40 mGy) implying a 30% radiation dose reduction. Images from the LD examinations were also postprocessed with a noise reduction software with non-linear filters (SharpView CT), creating filtered low dose images (FLD) for each patient. The three image stacks for each patient were presented side by side in randomized order. Five radiologists, blinded for dose level and filtering, ranked these three axial image stacks (ND, LD, FLD) as best to poorest (1 to 3) regarding three image quality criteria. Measurements of mean Hounsfield units (HU) and standard deviation (SD) of the HU were calculated for large region of interest in the centrum semiovale as a measure for noise., Results: Ranking results in pooled data showed that the advanced noise filtering significantly improved the image quality in FLD as compared to LD images for all tested criteria. No significant differences in image quality were found between ND examinations and FLD. However, there was a notable inter-reader spread of the ranking. SD values were 15% higher for LD as compared to ND and FLD., Conclusion: The advanced noise filtering clearly improves image quality of CT examinations of the brain. This effect can be used to significantly lower radiation dose.

Background: Characteristics of patients with community-acquired pneumonia (CAP) due to pandemic influenza A 2009 (H1N1) have been inadequately compared to CAP caused by other respiratory pathogens. The performance of prediction rules for CAP during an epidemic with a new infectious agent are unknown., Methods: Prospective, population-based study from November 2008-November 2009, in centers representing 70% of hospital beds in Iceland. Patients admitted with CAP underwent evaluation and etiologic testing, including polymerase chain reaction (PCR) for influenza. Data on influenza-like illness in the community and overall hospital admissions were collected. Clinical and laboratory data, including pneumonia severity index (PSI) and CURB-65 of patients with CAP due to H1N1 were compared to those caused by other agents., Results: Of 338 consecutive and eligible patients 313 (93%) were enrolled. During the pandemic peak, influenza A 2009 (H1N1) patients constituted 38% of admissions due to CAP. These patients were younger, more dyspnoeic and more frequently reported hemoptysis. They had significantly lower severity scores than other patients with CAP (1.23 vs. 1.61, P= .02 for CURB-65, 2.05 vs. 2.87 for PSI, P<.001) and were more likely to require intensive care admission (41% vs. 5%, P<.001) and receive mechanical ventilation (14% vs. 2%, P= .01). Bacterial co-infection was detected in 23% of influenza A 2009 (H1N1) patients with CAP., Conclusions: Clinical characteristics of CAP caused by influenza A 2009 (H1N1) differ markedly from CAP caused by other etiologic agents. Commonly used CAP prediction rules often failed to predict admissions to intensive care or need for assisted ventilation in CAP caused by the influenza A 2009 (H1N1) virus, underscoring the importance of clinical acumen under these circumstances.

Background. With modern CT imaging a comprehensive overview of cerebral macro- and microcirculation can be obtained within minutes in acute ischemic stroke. This opens for patient stratification and individualized treatment. Methods. Four patients with acute ischemic stroke of different aetiologies and/or treatments were chosen for illustration of the comprehensive CT protocol and its value in subsequent treatment decisions. The patients were clinically evaluated according to the NIHSS-scale, examined with the comprehensive CT protocol including both CT angiography and CT perfusion, and followed up by MRI. Results. The comprehensive CT examination protocol increased the examination time but did not delay treatment initiation. In some cases CT angiography revealed the cause of stroke while CT perfusion located and graded the perfusion defect with reasonable accuracy, confirmed by follow-up MR-diffusion. In the presented cases findings of the comprehensive CT examination influenced the treatment strategy. Conclusions. The comprehensive CT examination is a fast and safe method allowing accurate diagnosis and making way for individualized treatment in acute ischemic stroke.

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 6–15 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 strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio=2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio=3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.

Introduction: Varicella is a common disease with possible consequences. The disease is usually contracted in childhood and persistent antibodies are produced. Varicella vaccine is not widely used in Iceland. The aim of the study was to investigate the epidemiology of varicella in Icelandic children and it s complications. The results may prove important when deciding on varicella immunization in Iceland., Material and Methods: The study was retrospective cross sectional. Varicella antibodies were measured from children <18 years of age. Hospital records of children with varicella were evaluated., Results: Serum samples numbered 280. Varicella antibodies were present in 65% of children <1 year of age but in 10% of 1-2 year old children. Almost all children had antibodies before the age of ten and 97.5% of children >10 years had antibodies. Hospital admissions were 58, annual admissions were or 3.6/100,000 children <18 years. Bacterial infections, most frequently skin infections, were the most common complication, followed by cerebellar ataxia, dehydration and nutritional deficiency., Conclusion: Most children in Iceland contract varicella before the age of ten. Substantial complications were recorded. It is important to recognize varicella, it's complications, treatment options and explore whether varicella vaccination should be instigated in Iceland. Key words: varicella, epidemiology, complications, children, infants, immunization.

The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented. It has been postulated that genetic host factors may have contributed to this high mortality. We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts. The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week. Fatality proportions were highest among infants, young adults, and the elderly. A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates. The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution. Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively. The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively. In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived. Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.

Intracerebral injection of hamster neurotropic (HNT) measles virus in weanling Balb/C mice leads to an encephalitis, which is characterized by glial activation, behavioral seizures, selective neurodegeneration, and, after approximately 7 days, death. To provide a better understanding of the underlying molecular pathology, we studied seizure evolution by continuously monitoring electroencephalographic (EEG) activity, examined neuroglia and neurons histologically, and measured the brain content of glia-derived neuroactive metabolites of the kynurenine pathway of tryptophan degradation. Microglia and astrocytes were activated as early as postinoculation day (PID) 1, with reactive microglia lining the extent of the alveus. This was followed by a more extensive microglial activation that specifically outlined hippocampal pyramidal neurons in areas CA1-CA3 and by increases in the hippocampal levels of the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN). These changes preceded the onset of EEG seizures, which had a mean onset of 108 h after inoculation. Prominent hippocampal cell loss, demonstrated by Nissl- and silver staining, was apparent by PID 5. Thus, we speculate that early glial reactions to HNT inoculation result in the excess formation of 3-HK and QUIN, which in turn causes subclinical seizure activity, behavioral seizures, and, eventually, neurodegeneration. In addition to its conceptual implications, our study indicates that timely interventions modulating glial activation or 3-HK/QUIN synthesis may be of benefit in preventing or arresting seizure-induced neuronal damage.

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

At present eight hepatitis B virus (HBV) genotypes have been characterized: A to H. The most common genotype in Northern Europe is genotype A. So far there is no record of the specific HBV genotype distribution in Iceland. Iceland has a small population whose homogeneity has changed due to increasing migration during the past decades. The distribution of HBV genotypes in Iceland was analyzed using sera from 170 Icelandic patients. The samples were obtained before 1989, during an HBV epidemic among intravenous drug users in 1989 to 1992 and after 1994. A fragment of the HBV S-gene was amplified, sequenced and subjected to phylogenetic analysis. Among samples derived before 1989 genotypes A, C, and D were found. Most of the samples diagnosed during the epidemic belonged to genotype D and a smaller portion to genotype A. This suggests that the epidemic was most likely caused either by an endogenous HBV strain or by a strain imported from Europe or the USA. Among samples obtained after 1994, genotypes A to E and G were found, but the majority were of genotypes A, C, and D. This is consistent with an increase in migration and immigration from regions in Asia and Africa during the past 10 years. Thus, the changing prevalence of HBV genotypes in a small isolated community such as Iceland reflects the influence of migration and increasing contacts with regions outside the Western World., (Copyright (c) 2005 Wiley-Liss, inc.)

Variants of hepatitis C virus (HCV) from a single infected blood donor and 13 viraemic recipients who were traced were examined by sequencing and cloning to determine the extent of virus diversity in hypervariable region 1. Serum-derived viral isolates were studied from the donor when his HCV infection was discovered in 1993, in his recipients that year (0.3-5 years post-transfusion) and 5 years later in the donor and six viraemic recipients who were still alive. Viral variants of broad diversity were readily demonstrated in the baseline samples of the donor (nucleotide p-distance 0.130), but significantly less (P<0.00003) diversity was observed in the recipients' first samples (p-distances within recipients 0.003-0.062). In the first blood samples of the recipients, many of the viral variants identified were closely related to a strain variant from the donor. In follow-up samples drawn 5 years later from the donor and six recipients, the p-distance among donor clones had increased (0.172, P<0.0005) compared with the recipients, who displayed significantly narrower quasispecies (0.011-0.086). A common finding was that recipients of blood components processed from the same donation differed substantially in persisting HCV infectious sequence. Markedly few changes leading to changes of amino acids had occurred during follow-up in four of six recipients. These results question the significance of the development of viral variants as a necessary phenomenon in the evolution of HCV and pathogenesis of the disease.

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.

A total of 63 HIV-1 strains collected in Iceland during the years 1989-96 were typed into serotypes A-E using a peptide-based enzyme immunoassay. The majority of the strains were of serotype B (66.6%). 22.2% were untypeable by this method. Until 1993 only serotype B was found, but in 1993 and after that date other serotypes, especially E (7.9%) were detected, indicating the spread of serotypes previously confined to developing countries. This may reflect the increase in the number of Icelanders travelling to distant countries and the increased immigration into Iceland from developing countries.

This study describes the prevalence of hepatitisG virus (HGV) in Iceland, in blood donors and in persons with parenteral risk factors. Among 370 randomly selected Icelandic blood donors, the prevalence of HGV viraemia was 3.8%, whereas the prevalence of HGV antibodies in the same donor group was found to be 13.2%, thus indicating that at least 17% of blood donors in Iceland had previously been exposed to HGV. Previous exposure was seen in all age groups and also in older blood donors. Among intravenous drug users (IVDUs), the prevalence of HGV was much higher. Among 109 hepatitisC virus (HCV) antibody-positive serum samples collected in the years 1992-1997, 33. 9% were polymerase chain reaction (PCR)-positive for HGV and 48.6% had HGV antibodies. Thus, the pattern of HGV in IVDUs was similar to findings among IVDUs in other western countries. HGV viraemia was detected neither in 10 patients with haemophilia nor in five dialysis patients. However, six of the 10 haemophilic patients and one of the five dialysis patients had HGV antibody. In conclusion, unlike hepatitis C, which seems to have been introduced into Iceland relatively recently and has remained virtually confined to IVDUs, exposure to HGV is common among all age groups in the general population, suggesting that the virus has been prevalent in Iceland for much longer, making additional routes of transmission probable.

Mycoplasma pneumoniae is a common cause of respiratory tract infections in humans. The aim of the present study was to analyse the seroepidemiology of M. pneumoniae infections in Iceland during a 10-y period. A retrospective analysis of all serological diagnosis of M. pneumoniae infections at the Department of Medical Virology, National University Hospital in Reykjavík was performed. A total of 13,201 test results from 1987 to 1996 were reviewed and altogether 762 patients were found to have raised M. pneumoniae antibody titres, using a conventional complement fixation assay. Infections were most common amongst young people (< or=16 y) but a second peak in incidence was observed around the age of 35 y. Significant annual (p < 0.0001) and seasonal variations (p=0.0003) were observed; M. pneumoniae infections were most common during the winter period. Three major outbreaks with intervals of three to five years were observed during the observation period. Patients diagnosed during these outbreaks had higher M. pneumoniae titres than those found when infections were less frequent (p=0.0017). Furthermore, the middle aged and elderly patients (> 50 y) had significantly lower M. pneumoniae titres than younger patients (p=0.0014). The findings of this study show that M. pneumoniae infections have definite annual and seasonal variations and also confirm previous studies showing community outbreaks of M. pneumoniae infections every 3-5 y.

Background: We reported high levodopa use and prevalences of Parkinson's Disease (PD) in periodically, time-clustered, icelandic cohorts born after major whooping cough epidemics (MWCE)., Methods: In order to quantify a possible relationship between age at first post-birth MWCE and risk of PD we: 1) calculated cumulative incidences of PD during the period 1954-1963 in one-year Icelandic cohorts born between 1869 and 1927, using raw material from a reported survey; 2) identified MWCE from 1869 onwards in Iceland; 3) estimated cohort ages at onset of incidence period and at first MWCE; and 4) combined the above-mentioned information using log-linear models. In addition, we studied the prevalence of levodopa users in Icelandic birth cohorts during a recent period., Results: The curves of the above-mentioned incidences and prevalences in one-year birth-cohorts showed: 1) a similar, age-related, inverted V profile; and 2) a systematic notchy pattern, with peak values for one or both measurements for cohorts born during or after each of nine MWCE identified during the period 1869-1927. When 13 cohorts born in years with MWCE were excluded from the analysis, the risk of PD rose with age at first defined MWCE, with the linear increase being 8.4% per year (95% CI: -0.1-18.3%)., Conclusions: These results are consistent with reported effects of age at exposure in animal models of toxic parkinsonism, age-related changes in the dopamine receptor-GPT-binding protein-adenylatecyclase system observed in rats treated with pertussis toxin, and some PD epidemiological features. They suggest that pertussis neurotoxicity could be casually treated to PD worldwide.

According to antibody analysis, approximately two of every three intravenous drug users in Iceland have become infected with hepatitis C virus (HCV). In this study, serum samples from 55 HCV antibody-positive intravenous drug users (39 males and 16 females) were analyzed by polymerase chain reaction, and the viral strains were grouped into genotypes. Only three genotypes--1a, 3a, and 1b--were found among the drug users. Of 40 persons who were positive by polymerase chain reaction, 23 (57.5%) had type 1a, 15 (37.5%) had type 3a, and one (2.5%) had type 1b. One serum sample was untypeable. HCV viral RNA was detectable in 84.6% of the males and 43.7% of the females, which is a significant difference between the sexes (p < 0.01). In addition, 41 randomly selected HCV antibody-positive intravenous drug users (17 males and 24 females) were tested for HCV viral RNA with a commercially available polymerase chain reaction technique. In this subset of drug users, 76.4% of the males and 33.3% of the females had detectable HCV RNA in their serum, which is also a significant sex difference (p < 0.01). This study shows that two HCV genotypes predominate among intravenous drug users in Iceland, and the results indicate that women eliminate virus more effectively than men.

This study describes an outbreak of hepatitis B primarily among intravenous drug users in Iceland which has a population with a very low incidence of hepatitis B virus infection. The incidence of acute hepatitis B is generally low in the Nordic Countries, in the order of one to five cases per 100,000 people per year. Between 1989 and 1992 there was an outbreak of hepatitis B virus infection primarily among the intravenous drug user (IVDU) population in Iceland. At the Department of Medical Virology, University of Iceland there were 44 cases of acute hepatitis B identified during the peak year 1990, an incidence of 16.9 cases of acute hepatitis B per 100,000 people. 63.6% of these were known to be IVDUs. The seroprevalence of the hepatitis B core antibody (anti-HBc) marker was assessed among 1100 randomly selected individuals. The average prevalence of this marker was 2.9% and rose from zero at the age of 15 and younger to 6.5% at the age of 65 and older. Among IVDUs attending a detoxification clinic in 1990 the prevalence of the anti-HBc was 32%. In contrast, those attending the same clinic, due to alcoholism only, did not have a significantly higher prevalence of anti-HBc than the group used for comparison.

Eight antibody-positive individuals were detected among 12,000 blood donations during the first year of screening blood donors for hepatitis C virus (HCV) antibodies in Iceland. All 8 were found to have a history of intravenous drug abuse. Six of these 8 individuals had previously donated blood to 27 patients who could be traced and examined for HCV infection. The great majority (23/27, 85%) of the recipients had demonstrable HCV antibodies. Furthermore, RNA analysis with the polymerase chain reaction showed that all patients with HCV antibodies had HCV RNA in their serum and in one hemodialysis patient without HCV antibodies viral RNA could be demonstrated. Genotyping of the HCV strains showed that the genotype of the donor was also identified in all but one of the infected recipients of his/her blood or blood products. This study, therefore, substantiates high infectivity of the HCV by blood or blood factor donation and shows that viremic HCV antibody-negative individuals exist.

This study demonstrates a very high prevalence of antibodies to hepatitis C virus among Icelandic intravenous (i.v.) drug users. Of 152 identified i.v. drug users 95 (63%) were shown to have antibodies to the hepatitis C virus. In contrast the seroprevalence in the general Icelandic population is low, (0.2%). Almost all cases of hepatitis C virus infection in Iceland are due to i.v. drug use or to use of infected blood or blood products. Sporadic cases with unexplained modes of transmission, a significant portion of hepatitis C infections elsewhere, are virtually non-existent in Iceland. The results of this study are consistent with the hypothesis that the sporadic community-acquired cases could be caused by blood transfer due to bites from insect vectors such as mosquitoes which are not found in Iceland.

We examined the prevalence of IgE and IgG4 class antibodies to the saliva of Aedes communis and Aedes aegypti mosquitoes in the sera of three groups of exposed children using a sensitive immunoblot method. The frequencies of IgE antibodies to the major 36-kD A. communis and A. aegypti saliva antigens ranged from 82 to 90% in the 20 Finnish, 17 Kenyan, and 20 Mexican children. The corresponding IgG4 antibody frequencies were 85, 41, and 20%, respectively. The nonexposed 20 Icelandic children did not show IgE or IgG4 antisaliva antibodies. Several of the Finnish children showed also IgE and IgG4 antibodies to a 22-kD A. communis saliva antigen. The Finnish children abnormally sensitive to mosquito bites had frequently IgE and IgG4 antibodies to the 22-kD A. communis saliva antigen, suggesting that these antibodies play a role in the pathogenesis of immediate cutaneous mosquito bite reactions. In contrast to this, no increase was found in the A. aegypti antibody frequencies in the Kenyan and Mexican children with papular urticaria, suggesting that humoral immune response to A. aegypti saliva is not involved in the development of this disorder. The present results show that humoral IgE and IgG4 immune responses to Aedes mosquito saliva antigens is common in children living both in temperature and tropical zones. The IgE antibodies seem to be involved in the immediate mosquito bite whealing, and the occurrence of the IgG4 subclass antisaliva antibodies might be an indicator of intense mosquito bite exposure.

In order to examine the status of quinolinic acid (QUIN) metabolism in a model of delayed excitotoxic neurodegeneration, the de novo production of QUIN from 3-hydroxyanthranilic acid was assessed in brain homogenates and brain slices of mice injected with hamster neurotropic measles virus. In the hippocampus, which presents exclusive nerve cell loss in this model, the activity of 3-hydroxyanthranilic acid oxygenase, an astrocytic enzyme responsible for the biosynthesis of QUIN, was increased 3.3-fold by 7 days after virus inoculation. Less dramatic increases were observed in the cerebral cortex and the striatum, while cerebellar enzyme activity was not different from control values. In the same brain homogenates, no changes occurred in the activities of kynurenine aminotransferase, the biosynthetic enzyme of the neuroprotectant kynurenic acid, and of the astrocytic marker glutamine synthetase. At 7 days postinoculation, hippocampal slices from virus-treated animals, when exposed to 3-hydroxyanthranilic acid, produced 18 times more QUIN than slices from control animals. Notably, a significant increase was also seen 3 days postinoculation, i.e., at a time when astrocytes had started to proliferate but prior to the onset of neurodegeneration (Eur. J. Neurosci. 3:66-71, 1991). These data suggest that astrocyte-derived QUIN may play a causative role in the occurrence of hippocampal nerve cell loss in measles virus-infected mice.

The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in Balb/c mice, associated with neurodegeneration in hippocampal CA1 and CA3 regions. This loss of pyramidal cells can be prevented by twice daily systemic treatment with 1 mg/kg dizocilpine (5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate; MK-801) for 7 days. By varying the MK-801 treatment protocol, we now found that drug administration during the last 4 days prior to sacrifice (i.e. days 4-7 post inoculation, p.i.) is essential for neuroprotection. In contrast, MK-801 treatment during the first days (days 0-4 p.i.) did not prevent the neuronal necrosis. These data suggest that the concentration of an excitotoxic factor in the mouse brain increases after virus inoculation, reaching toxic levels by days 4-5 p.i. This novel 'subacute' mouse model of neurodegeneration therefore constitutes an attractive tool for mechanistic and interventional studies in excitotoxicity research.

Progressive states of maturing lentivirus: maedia visna virus (MVV) and human immunodeficiency virus (HIV), respectively, have been visualized by 2-D electron microscopy and by 3-D electron microscopic tomography. A major fraction of MVV and a low percentage of HIV appear as immature particles 4 to 5 days post virus infection. Upon budding the gag-precursor material is densely packed inside the external envelope. After virus release the major portion of precursors is assembled within an approximately 25 nm thick layer directly attached to the envelope. Structural maturation of the core is different for the two viruses. Pleomorphic cores are observed in mature MVV in contrast to structurally defined cores of HIV. The latter are principally cone-shaped, spanning the entire diameter of the virion with a 40 to 60 nm wide free end and an approximately 20 nm narrow end attached to the envelope with a core-envelope-link.