Magnus Gottfredsson

BACKGROUND: Candidaemia places a substantial burden on healthcare systems. Long-term, population-based studies of candidaemia rates with appropriate adjustments for changes in age composition are lacking. AIM: We aimed to determine trends in candidaemia incidence rates, species distribution, antifungal susceptibility, and concurrent antifungal use in Iceland between 2012 and 2023, as well as long-term (2000–2023) trends in age-standardised incidence rates (ASRs). METHODS: We analysed patient data with blood cultures positive for Candida species, or yeasts previously assigned to the genus Candida . We calculated ASRs, standardised to the 2023 Icelandic population, and performed susceptibility testing on all available isolates. RESULTS: Overall, we identified 207 candidaemia episodes in 193 patients. The average ASR was 5.2 cases per 100,000 population. The ASR increased significantly from 2012 to 2023 (incidence rate ratio (IRR) = 1.07; p = 0.001), mainly driven by increased rates among males (IRR = 1.10; p = 0.001). From 2000 to 2023, the ASR remained stable (average 5.8/100,000; IRR = 1.00). The ASR was higher among males, both during 2012–2023 (p = 0.014) and long-term (2000–2023, p = 0.001). Age-specific incidence rate was highest among > 80-year-old males (44.0/100,000). Candida albicans was the most frequent species (41.0%), followed by Nakaseomyces glabratus (27.2%) and Candida tropicalis (11.1%). Fluconazole susceptibility remained high ( C. albicans 99%, C. tropicalis 75%, Candida parapsilosis 100%), and echinocandin resistance was rare (1.9%). CONCLUSION: Despite an apparent increase from 2012 to 2023, candidaemia incidence in Iceland has remained stable in a long-term (24-year) perspective, when appropriate adjustments are made for the ageing population. Concurrently, the epidemiology has shifted towards non- albicans Candida infections.

Background: The nationwide Treatment as Prevention program for Hepatitis C (TraP HepC) was initiated in Iceland in 2016, where direct-acting antivirals (DAAs) replaced interferon-based treatments for hepatitis C virus (HCV). The study aimed to assess the impact of TraP HepC on the epidemiology of HIV/HCV coinfection, the cascade of care, and HCV reinfection rates among coinfected individuals. Methods: A nationwide retrospective study was conducted on all people with HIV in Iceland who tested HCV antibody positive during 2000–2020. Medical records, laboratory results, and treatment outcomes were reviewed and analyzed by treatment era: interferon (2000–2015) and DAA (2016–2020). Results: Out of 648 people with HIV, 78 were HCV antibody positive during 2000–2020, of whom 61 had confirmed HCV viremia. The total number of HIV/HCV-coinfected individuals increased steadily, peaking at 41 in 2016, but decreased by >85% to 6 by 2020 following the nationwide TraP HepC program. In total, 84 active HCV infections including reinfections were diagnosed, which prompted 81 treatment initiations and yielded 66 cures. During the interferon era, 45% (13/29) achieved cure, compared with 88% (53/60; P < .001) in the DAA era. The HCV reinfection rate in this group was 9.35/100 person-years, all presumed to be acquired by injection drug use. Conclusions: Before the nationwide elimination campaign, the incidence of HIV/HCV coinfections was steadily increasing, but it has subsequently decreased by >85%, primarily due to the widespread use of DAAs. However, high reinfection rates in this population suggest that ongoing prevention, early diagnosis, and easy access to DAAs are necessary to maintain success.

Background: Streptococcus pneumoniae is a major global cause of invasive pneumococcal disease (IPD) and death. Introduction of the pneumococcal conjugate vaccine (PCV) has led to substantial declines in IPD incidence in many countries. Long-term, population-based studies on mortality trends among survivors of acute IPD are scarce. Methods: Data encompassing all individuals diagnosed with IPD in Iceland from 1975 to 2020 were analyzed. Diagnosis required a positive blood or cerebrospinal fluid culture. 30-day and 5-year mortality rates were assessed across 3 decades (1985–2014), adjusting for multiple covariates. Additionally, age-standardized all-cause mortality rates were compared between patients with IPD and the general population. Results: The cohort included 1463 patients of all ages. Invasive pneumococcal disease incidence peaked in 1995–2004 and declined significantly thereafter (P < .001). Serotype 7F was the most prevalent. No improvement in short-term mortality at 30 days was detected over time (P = .98). A modest improvement in 5-year mortality was observed, although this did not reach statistical significance (P = .076). Even when early deaths were excluded, the ASR for all-cause mortality in patients with IPD was 2.6 times higher than in the general population (0.021 vs 0.008 per person-year). Conclusions: IPD incidence declined substantially over time, particularly following the introduction of the 10-valent PCV in 2011, yet short-term mortality remained unchanged. A modest improvement in long-term mortality was observed, possibly reflecting advances in chronic disease management. Invasive pneumococcal disease survivors face significantly elevated long-term mortality compared to the general population. Targeted interventions are needed to reduce short-term mortality associated with IPD.

Background/Objectives: The rising demand for total joint arthroplasty (TJA) and increasing incidence of prosthetic joint infections (PJIs) significantly burden patients and healthcare systems. This retrospective study describes the epidemiology, clinical characteristics and outcomes of PJIs in Iceland from 2003 to 2020. Methods: PJI cases were identified through synovial fluid cultures and ICD codes, with classification per EBJIS criteria. Unlikely cases were excluded. Results: Among 293 cases with a mean age of 70 years, 60% (176/293) were males and 58% (171/293) involved the knee. Over half of infections occurred within two years post TJA, with an incidence rate of 0.94%, increasing significantly over time (p = 0.012). Males had significantly higher incidence rates than females (incidence rate ratio 0.42; p < 0.001). The most common pathogens were coagulase-negative staphylococci (30%, 88/293), and 9% (27/293) of cases were culture-negative. DAIR was the first-line treatment in about 50% (147/293) of cases but it failed in nearly half, contributing to an overall treatment failure rate of 38% (98/259). PJI-related mortality was 2% (6/293). Conclusions: The results indicate an increased incidence, with the highest risk within two years of TJA. Males are at greater risk, while females more commonly undergo TJA. DAIR success rates were lower than reported elsewhere but improved significantly over time. Better methods to prevent PJIs are needed.

Background/Objectives: Direct-acting antiviral (DAA) therapy has been highly successful in treating chronic hepatitis C (CHC). The nationwide Treatment as Prevention of Hepatitis C (TraP HepC) initiative that was launched in Iceland in 2016 utilized liver stiffness measurements (LSM) to assess liver fibrosis at baseline and follow-up. We aimed to determine changes in liver stiffness among patients following treatment with DAAs and evaluate risk factors associated with hepatic fibrosis. Methods: Eligible CHC patients with liver stiffness of >9.5 kilopascals (kPa) before DAA treatment were invited for a follow-up visit in 2024. Risk factors for cirrhosis were registered, LSM performed, and liver enzymes, blood lipids, and glucose levels measured. Changes in liver stiffness were compared to baseline measurements, and correlations with risk factors were analyzed. Results: A total of 96 patients had LSMs > 9.5 kPa at treatment initiation. During the follow-up period, 61 were eligible for participation, 38 consented, and 34 (35%) died. The total follow-up was 258.3 person-years. The median follow-up period between measurements was 7.1 years. The median liver stiffness decreased from 17.2 kPa to 7.3 kPa (p < 0.01), and 80% of those with cirrhosis (>12.5 kPa) regressed to non-cirrhotic values. High BMI and daily alcohol consumption were significantly associated with increased liver stiffness in 8% of patients. Conclusions: In this single-arm, pre-post pilot study, liver stiffness regressed significantly in 92% of patients who were cured of CHC. Patients with other persistent risk factors following cure, such as obesity and alcohol abuse, were the only patients who had increased liver stiffness at the end of follow-up.

The aim of this study was to collect data and analyze mortality among patients hospitalized with community-acquired infections in the Faroe Islands. A prospective observational study was conducted in the Medical Department of the National Hospital of the Faroe Islands from October 2013 to April 2015. Cumulative all-cause, in-hospital, short-term, intermediate-term and long-term mortality rates were calculated. Kaplan–Meier survival curves comparing infection-free patients with infected patients of all severities and different age groups are presented. A log-rank test was used to compare groups. Mortality hazard ratios were calculated for subgroups using Cox regression multivariable models. There were 1309 patients without infection and 755 patients with infection. There were 51% female and 49% male patients. Mean age was 62.73 ± 19.71. Cumulative all-cause mortality and in-hospital mortality were highest in more severe forms of infection. This pattern remained the same for short-term mortality in the model adjusted for sex and age, while there were no significant differences among the various infection groups in regard to intermediate- or long-term survival after adjustment. Overall and short-term mortality rates were highest among those with severe manifestations of infection and those with infection compared to infection-free patients.

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Background: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. Methods: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5–18 months after infection. Results: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. Conclusions: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Aims: We aimed to compare COVID-19 control measures, epidemiological characteristics and economic performance measures in two high-income island nations with small populations, favorable border control options, and relatively good outcomes: Iceland and New Zealand (NZ). Methods: We examined peer-reviewed journal articles, official websites, reports, media releases and press articles for data on pandemic preparedness and COVID-19 public health responses from 1 January 2020 to 1 June 2022 in Iceland and NZ. We calculated epidemiological characteristics of the COVID-19 pandemic, as well as measures of economic performance. Results: Both nations had the lowest excess mortality in the OECD from the start of the pandemic up to June 2022. Iceland pursued a mitigation strategy, never used lockdowns or officially closed its border to foreign nationals, and instead relied on extensive testing and contact tracing early in the pandemic. Meanwhile, NZ pursued an elimination strategy, used a strict national lockdown to stop transmission, and closed its international border to everyone except citizens and permanent residents going through quarantine and testing. Iceland experienced a larger decrease in gross domestic product in 2020 (relative to 2019) than NZ (–8·27% vs. –1·22%, respectively). In late 2021, NZ announced a shift to a suppression strategy and in 2022 began to reopen its border in stages, while Iceland ended all public restrictions on 25 February 2022. Conclusions: Many of Iceland’s and NZ’s pandemic control measures appeared successful and features of the responses in both countries could potentially be adopted by other jurisdictions to address future disease outbreaks and pandemic threats.