Molecular benchmarks of a SARS-CoV-2 epidemic.

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.

Cell-phone traces reveal infection-associated behavioral change.

Epidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; [Formula: see text]), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; [Formula: see text]) while spending longer on the phone (41- to 66-s average increase; [Formula: see text]) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited.

Humoral Immune Response to SARS-CoV-2 in Iceland.

BACKGROUND: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Spread of SARS-CoV-2 in the Icelandic Population.

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.).

Flying, phones and flu: Anonymized call records suggest that Keflavik International Airport introduced pandemic H1N1 into Iceland in 2009.

BACKGROUND: Data collected by mobile devices can augment surveillance of epidemics in real time. However, methods and evidence for the integration of these data into modern surveillance systems are sparse. We linked call detail records (CDR) with an influenza-like illness (ILI) registry and evaluated the role that Icelandic international travellers played in the introduction and propagation of influenza A/H1N1pdm09 virus in Iceland through the course of the 2009 pandemic. METHODS: This nested case-control study compared odds of exposure to Keflavik International Airport among cases and matched controls producing longitudinal two-week matched odds ratios (mORs) from August to December 2009. We further evaluated rates of ILI among 1st- and 2nd-degree phone connections of cases compared to their matched controls. RESULTS: The mOR was elevated in the initial stages of the epidemic from 7 August until 21 August (mOR = 2.53; 95% confidence interval (CI) = 1.35, 4.78). During the two-week period from 17 August through 31 August, we calculated the two-week incidence density ratio of ILI among 1st-degree connections to be 2.96 (95% CI: 1.43, 5.84). CONCLUSIONS: Exposure to Keflavik International Airport increased the risk of incident ILI diagnoses during the initial stages of the epidemic. Using these methods for other regions of Iceland, we evaluated the geographic spread of ILI over the course of the epidemic. Our methods were validated through similar evaluation of a domestic airport. The techniques described in this study can be used for hypothesis-driven evaluations of locations and behaviours during an epidemic and their associations with health outcomes.

Modelling the elimination of hepatitis C as a public health threat in Iceland: A goal attainable by 2020.

BACKGROUND & AIMS: In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization's HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring. METHODS: We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections. RESULTS: The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely. CONCLUSION: HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached. LAY SUMMARY: In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur.

Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

Benefits of Water Safety Plans: microbiology, compliance, and public health.

The Water Safety Plan (WSP) methodology, which aims to enhance safety of drinking water supplies, has been recommended by the World Health Organization since 2004. WSPs are now used worldwide and are legally required in several countries. However, there is limited systematic evidence available demonstrating the effectiveness of WSPs on water quality and health. Iceland was one of the first countries to legislate the use of WSPs, enabling the analysis of more than a decade of data on impact of WSP. The objective was to determine the impact of WSP implementation on regulatory compliance, microbiological water quality, and incidence of clinical cases of diarrhea. Surveillance data on water quality and diarrhea were collected and analyzed. The results show that HPC (heterotrophic plate counts), representing microbiological growth in the water supply system, decreased statistically significant with fewer incidents of HPC exceeding 10 cfu per mL in samples following WSP implementation and noncompliance was also significantly reduced (p < 0.001 in both cases). A significant decrease in incidence of diarrhea was detected where a WSP was implemented, and, furthermore, the results indicate that population where WSP has been implemented is 14% less likely to develop clinical cases of diarrhea.

International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005.

The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.

[The use of anti-viral agents in pandemic influenza, Icelandic guidelines]. / Veirulyf gegn inflúensu og leibeiningar um notkun eirra í heimsfraraldri.

Intensive work on preparedness planning for the next pandemic influenza is currently ongoing in Iceland as well as in other countries. Anti-viral agents will play a significant role in minimizing the potential devastating effects of pandemic influenza. In this overview the antivirals likely to be used in the next pandemic influenza are discussed and official national guidelines provided regarding their use. In order to maximize the utilization of the national stockpiles of antiviral agents the authors hope that icelandic physicians will follow the guidelines presented.

Clinical experience of urine D-arabinitol/L-arabinitol ratio in the early diagnosis of invasive candidiasis in paediatric high risk populations.

In 2 prospective studies, we previously reported on the early and accurate diagnosis of invasive candidiasis by determining the D-arabinitol/L-arabinitol (DA/LA) ratio in urine in neutropenic children with cancer at the paediatric oncology unit (POU) and in premature infants at the neonatal intensive care unit (NICU) at our hospital. In this retrospective study at the same units, we report how the DA/LA assay was implemented in clinical practice immediately after the prospective study periods. We found that, in the POU, the recommendation of regularly monitoring urine DA/LA ratios in patients at risk and considering antifungal therapy in the case of elevated ratios had been followed. A significant decrease in the incidence of culture positive invasive candidiasis may have been attributed to the introduction of the DA/LA assay. At the NICU, where the DA/LA assay was recommended only as an adjunct to other diagnostic tools, morbidity in invasive candidiasis remained unchanged. While regular monitoring of the urine DA/LA ratio probably facilitates the early detection of invasive candidiasis in paediatric oncology, it remains to be determined if the test can be used in a similar way in neonatal intensive care.

[Scombroid poisoning at an Icelandic restaurant]. / Krílfiskieitrun á íslenskum veitingastad.

We report four cases of scombroid poisoning. During a lunch meeting three males had the same dish: a club sandwich with raw tuna. All developed erythema over the face and neck within two hours of eating the tuna. The severity of symptoms varied. Other symptoms were profuse sweating, a feeling of intense thirst and palpitations. The symptoms disappeared after few hours. Samples obtained from the tuna revealed histamine levels above the recommended FDA levels. We also report a case with similar symptoms after eating canned tuna in a mixed salad. Scombroid poisoning has been associated with the consumption of dark-flesh fish with high levels of histidine, which can be converted to histamine by decarboxylase from Gram-negative bacteria in the fish. The fish most often implicated is tuna. It is of great importance to increase the awareness of this type of poisoning for correct diagnosis and to prevent other cases by improving storage.

Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection.

Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here.