Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents.

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.

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.

Regulation of local availability of active tissue-type plasminogen activator in vivo in man.

Free, biologically active tissue-type plasminogen activator (tPA) is the main initiator of intravascular fibrinolysis, but little is known about the regulation of active tPA on the organ level. The aim was to investigate if the local availability of active tPA on the organ level depends on the local release rate of tPA or the arterial input of tPA and plasminogen activator inhibitor type 1 (PAI-1). Also, we wanted to evaluate if plasma levels predict capacity for endothelial release of fibrinolytic proteins. Invasive perfused-forearm studies were performed in 96 healthy subjects. Local release rates of fibrinolytic proteins were assessed at baseline and during endothelial stimulation. Stimulation by methacholine and desmopressin induced a 6- and 12-fold increase in total tPA release rates, respectively. With increasing local release rates of tPA a gradually closer correlation emerged between the total tPA secretion and the forearm output of active tPA (from r = 0.102, ns to r = 0.85, P < 0.0001). Forearm availability of active tPA was not related to arterial input of either tPA or PAI-1. Release rates and plasma levels of tPA were not correlated. Baseline release rates of active tPA increased to noon. The major determinant for the local availability of active tPA is the capacity of the endothelium to release tPA rather than the arterial input of PAI-1 or tPA. Despite a molar excess of PAI-1, the majority of tPA released during stimulation does not undergo local inactivation. The capacity to release tPA locally cannot be predicted from its plasma concentration.

Ganciclovir treatment of cytomegalovirus disease in immunocompromised children.

Twelve immunocompromised children were treated with 13 courses of intravenously administered ganciclovir for severe cytomegalovirus disease. All children were allograft recipients; 6 received organ transplants (5 liver, 1 kidney) and 6 received bone marrow. They presented with one or more of the following forms of cytomegalovirus disease: pneumonitis, 9; hepatitis, 3; colitis, 2; peritonitis, 1; and retinitis, 1. Clinical improvement was observed in 7 (58%) of 12 patients during ganciclovir therapy. Cessation of active viral replication during therapy accompanied 69% of the treatment courses. Mild and transient increases in creatinine and liver function tests and/or decreases in neutrophil count accompanied 77% of treatment courses but neutropenia (less than 1000 cells/mm3) did not occur. Transient decreases in platelet counts accompanied therapy in 3 bone marrow allograft recipients, but greater than 50% decrease in lymphocyte count was not seen. We conclude that ganciclovir is safe and appears to have a beneficial effect on cytomegalovirus disease in some pediatric transplant recipients.

Immune responses of infants vaccinated with serotype 6B pneumococcal polysaccharide conjugated with tetanus toxoid.

BACKGROUND: Streptococcus pneumoniae is a major cause of meningitis, bacteremia, pneumonia and otitis media. Pneumococcal polysaccharides are not immunogenic in infants, but improved immunogenicity of polysaccharide-protein conjugates has been demonstrated. Antibiotic-resistant pneumococci have increased the need for an effective vaccine. OBJECTIVE: To study the safety and immunogenicity of a pneumococcal type 6B polysaccharidetetanus toxoid conjugate (Pn6B-TT) in infants and to assess the function of antibodies. METHODS: Healthy infants were injected, Group A at 3, 4 and 6 months (n = 21) and Group B at 7 and 9 months (n = 19). Booster injection was given at 18 months. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and functional activity was measured by opsonization of radiolabeled pneumococci. Nasopharyngeal cultures were obtained. RESULTS: No significant adverse reactions were observed. Pn6B-IgG (enzyme-linked immunosorbent assay) increased to a geometric mean of 0.62 microgram/ml (P = 0.367, compared with prevaccination titers) in Group A at 7 months and 1.22 micrograms/ml (P < 0.001) in Group B at 10 months. Total Pn6B antibodies (radioimmunoassay) were 44 ng of antibody N/ml (P < 0.053) in Group A and 211 ng of antibody N/ml (P < 0.001) in Group B. A smaller increase in IgM and IgA anti-Pn6B was observed. Reinjection at 18 months elicited booster responses in total and IgG anti-Pn6B; 62% of those in Group A and 79% of those in Group B had > 300 ng of antibody N/ml. Opsonic activity, after initial and booster vaccinations, correlated with Pn6B-antibody titers. Three infants with nasopharyngeal cultures repeatedly positive for serogroup 6 had poor serum IgG responses. CONCLUSION: Our results demonstrate that Pn6B-TT is safe, elicits functional antibodies and memory responses in infants.

Comparison of interventional cardiology in two European countries: a nationwide Internet based registry study.

BACKGROUND: The practice of interventional cardiology differs between countries and regions. In this study we report the results of the first nation-wide long-term comparison of interventional cardiology in two countries using a common web-based registry. METHODS: The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to prospectively and continuously collect background-, quality-, and outcome parameters for all coronary angiographies (CA) and percutaneous coronary interventions (PCI) performed in Iceland and Sweden during one year. RESULTS: The rate of CA per million inhabitants was higher in Iceland than in Sweden. A higher proportion of patients had CA for stable angina in Iceland than in Sweden, while the opposite was true for ST elevation myocardial infarction. Left main stem stenosis was more commonly found in Iceland than in Sweden. The PCI rate was similar in the two countries as was the general success rate of PCI, achievement of complete revascularisation and the overall stent use. Drug eluting stents were more commonly used in Iceland (23% vs. 19%). The use of fractional flow reserve (0.2% vs. 10%) and the radial approach (0.6% vs. 33%) was more frequent in Sweden than in Iceland. Serious complications and death were very rare in both countries. CONCLUSION: By prospectively comparing interventional cardiology in two countries, using a common web based registry online, we have discovered important differences in technique and indications. A discovery such as this can lead to a change in clinical practice and inspire prospective multinational randomised registry trials in unselected, real world populations.

Kingella kingae infections in paediatric patients: 5 cases of septic arthritis, osteomyelitis and bacteraemia.

Kingella kingae is a Gram-negative rod most often recognized as 1 of the organisms causing septic arthritis and osteomyelitis in children. Infection caused by K. kingae had not been diagnosed in Iceland until 5 cases were diagnosed at the Paediatric Department at the University Hospital of Iceland over a 1 year period. In this report we describe these 5 children with invasive infection caused by K. kingae (2 with septic arthritis, 1 with osteomyelitis, 1 with septic arthritis and osteomyelitis, and 1 with bacteraemia) and review the literature. All bacterial isolates were identified by the Bactec culture system.

[Kingella kingae ostemyelitis and septic arthritis in paediatric patients. Six cases from the Department of Pediatrics, National University Hospital of Iceland.].

Kingella kingae (K. kingae) is a gram negative rod most often associated with septic arthritis and osteomyelitis in children. Infections caused by K. kingae had not been reported in Iceland when six cases were diagnosed at the Pediatric Department at the National University Hospital of Iceland. In this report we describe those cases and review the literature.

[Immediate PTCA for acute myocardial infarction in Iceland.].

In recently published articles it has been possible to show better results with primary immediate PTCA (percutaneous transluminal coronary angioplasty) than thrombolysis in acute myocardial infarction. This method also has advantages for patients after failed thrombolysis and if thrombolysis is contraindicated. Further advantages are fewer in-hospital days and lower follow-up costs. In this article we discuss immediate PTCA in Iceland and present a follow-up of all patients that underwent this procedure during the first year it was performed in this country. Our conclusion is that immediate PTCA was successfully carried out during the first year it was performed in Iceland.

Disseminated infection with Fusarium in recipients of bone marrow transplants.

Clinical data from 10 episodes of disseminated infection with Fusarium among eight recipients of bone marrow transplants and from 31 cases reported previously in the literature were analyzed in an effort to characterize the natural history of this rare infection and its response to therapy. The characteristic signs of fusarial infection--disseminated skin nodules, fungemia, and multiple-organ involvement--are results of its propensity for early spread. From a review of the literature and our own experience, it appears that recovery of phagocytic mechanisms (the primary immunologic defenses against Fusarium) in the form of rising neutrophil counts is mandatory for clinical resolution. Even after a graft begins to function adequately, Fusarium may not be completely eradicated, as evidenced by the high incidence of recurrence among patients with subsequent neutropenic episodes. Fusarium is highly resistant to conventional antifungal drugs in vitro, but its progression may be slowed by intensive antifungal therapy until the recovery of adequate neutrophil levels.

[The ΔF508 mutation in cystic fibrosis patients].

Cystic fibrosis is a serious autosomal recessive disorder. It is commonest among the white Caucasian populations in North and Western Europe. However, no information is available on this disease in Iceland. Only 21 patients have been diagnosed with this condition in Iceland since 1958, hence the prevalence is estimated to be around 1/7000. Three young children, aged 6-30 months, with clinical symptoms suggestive of cystic fibrosis: namely recurrent respiratory infections, malabsorption of fat, low trypsin and chymotrypsin activity and positive sweat test, were investigated. Mutational analysis revealed that all three children were homozygous for the AF508 mutation in the cystic fibrosis gene. This is the first report of cystic fibrosis in Iceland. It is expected that 2-3% of the population are carriers of cystic fibrosis. Identification of all disease-causing mutations in the population should be feasible and encouraged.

[Icelandic boy with Lyme-disease. A case report and discussion.].

Lyme-disease is an infection involving many organ systems and is caused by the spirochete Borrelia burgdorferi. Lyme-disease is the most prevalent vector-born disease in the United States and also occurs in parts of Europe and Asia. However, to the best of our knowledge, Lyme-disease has not been described in Iceland before. In this article we report a 14-year-old, Icelandic boy with arthritis due to Lyme-disease. Lyme-disease was described as a separate entity in 1976. The identification of a novel spirochete B. burgdorferi as the responsible organism was made in 1982. The disease is a multisystem illness, but erythema migrans is the clinical hallmark of Lyme-disease. It can also affect the skin, eyes, musculoskeletal tissue, nervous system and heart. Diagnosis should rest on a careful history and objective clinical findings, supported by appropriately chosen laboratory tests. All stages of Lyme-disease respond to appropriate antibiotic therapy. It is important that Icelandic physicians be aware of Lyme-disease.

[Fungemia and other invasive fungal infections in Icelandic children. A nationwide study.].

INTRODUCTION: Invasive fungal infections are increasing in incidence. Among those who are at increased risk of fungal blood stream infections (fungemia) and disseminated fungal infections are premature infants and immunosuppressed children. These infections are associated with high morbidity and mortality. Invasive fungal infections have not yet been studied in Iceland. MATERIAL AND METHODS: We studied all cases of fungemia and/or disseminated fungal infections in Icelandic children (16 years) during a 20 year period. Histopathology reports and autopsies were reviewed. Information on predisposing factors, symptoms, treatment and outcome was collected. All obtainable fungal blood stream isolates were subcultured and their susceptibility to common antifungals determined. RESULTS: In the 20 year period from 1980-1999, 19 episodes of invasive fungal infections were diagnosed in 18 infants and children in Iceland. Twelve episodes of fungemia occured in 11 children and the nationwide annual incidence increased from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of the children were premature infants. All patients had a central venous catheter at the time of blood culture and most had received intravenous antibiotics or corticosteroids. Candida albicans was the most commonly isolated species (nine of 12 episodes, 75%). In addition to patients with fungemia, three children were diagnosed with disseminated fungal infection by histology or autopsy. Two cases of fungal meningitis, without fungemia, were identified. Furthermore, two children had invasive infections with Aspergillus fumigatus and both patients survived. Three children (3/16; 19%) with invasive Candida-infections died. CONCLUSIONS: In this study of invasive fungal infections among Icelandic children we demonstrate that the incidence of fungemia has risen significantly in the past 20 years. Diagnosis of invasive fungal infections can be complicated and negative blood cultures do not exclude disseminated infection. Given the high attributable mortality, timely diagnosis and aggressive treatment is extremely important.

Isotypes and opsonophagocytosis of pneumococcus type 6B antibodies elicited in infants and adults by an experimental pneumococcus type 6B-tetanus toxoid vaccine.

Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741, r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.