Real-time, portable genome sequencing for Ebola surveillance.

The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10(-3) and 1.42 × 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned.

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March-September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

High impact of molecular surveillance on hepatitis A outbreak case detection in Sweden: a retrospective study, 2009 to 2018.

BackgroundSwedish hepatitis A surveillance includes sequence-based typing, but its contribution to outbreak detection in relation to epidemiological investigations has not been fully evaluated.AimTo evaluate the role of sequence-based typing in hepatitis A outbreak detection and to describe the hepatitis A epidemiology in Sweden to improve surveillance.MethodsWe retrospectively investigated hepatitis A virus sequences of 447 cases notified in Sweden 2009-18. We performed a phylogenetic analysis of evolutionary distances to identify cases with similar virus sequences (≥ 459/460 identical nt in the VP1/P2A junction). Unique sequences, dyads and sequence-based clusters (SBCs) were identified. We linked non-sequenced cases by epidemiological information and retrospectively assessed the value of typing for outbreak identification.ResultsFifty-five percent (n = 542/990) of the notified hepatitis A cases were referred to the Public Health Agency of Sweden for typing and 447 (45%) were sequenced successfully. Subgenotypes included IA (42.5%, n = 190), IB (42.7%, n = 191) and IIIA (14.8%, n = 66). Phylogenetic analysis identified 154 unique sequences, 33 dyads (66 cases) and 34 SBCs (227 cases). The combination of molecular and epidemiological data revealed 23 potential outbreaks comprising 201 cases. Cases were linked by sequence (59%, n = 118), epidemiological data (11%, n = 23) or both (30%, n = 60). Typing was needed to identify 15 of 23 potential outbreak signals.ConclusionSequence-based typing contributed substantially to detecting clustering cases and identifying outbreaks in Sweden. The results show routine sequence-based typing detects outbreaks, promotes timely outbreak investigations and facilitates international collaboration.

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021.

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45-74) for one dose only and 89% (95% CI: 79-94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Systematic Review of Whole-Genome Sequencing Data To Predict Phenotypic Drug Resistance and Susceptibility in Swedish Mycobacterium tuberculosis Isolates, 2016 to 2018.

In this retrospective study, whole-genome sequencing (WGS) data generated on an Ion Torrent platform was used to predict phenotypic drug resistance profiles for first- and second-line drugs among Swedish clinical Mycobacterium tuberculosis isolates from 2016 to 2018. The accuracy was ∼99% for all first-line drugs and 100% for four second-line drugs. Our analysis supports the introduction of WGS into routine diagnostics, which might, at least in Sweden, replace phenotypic drug susceptibility testing in the future.

Outbreak of gastroenteritis highlighting the diagnostic and epidemiological challenges of enteroinvasive Escherichia coli, County of Halland, Sweden, November 2017.

An outbreak of gastroenteritis with 83 cases occurred at a conference venue in November 2017 in Halland County, Sweden. Stool samples from two venue visitors and a symptomatic secondary case attributed to household transmission were PCR-positive for the ipaH gene, a target found in both Shigella spp. and enteroinvasive Escherichia coli (EIEC). EIEC was isolated from stool samples and whole genome sequencing analysis confirmed EIEC O96:H19 to be the aetiological agent. A cohort study was conducted among venue attendees and employees and the findings implicated contaminated leafy greens as the vehicle of infection, however, no microbiological evidence could support the study results. Here, we report the investigation into the first recorded EIEC outbreak in Sweden and illustrate the challenges associated with the differential laboratory diagnostics of Shigella/EIEC in an outbreak setting.

Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study.

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. RESULTS: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Novel influenza A(H1N2) seasonal reassortant identified in a patient sample, Sweden, January 2019.

In January 2019, a human seasonal reassortant influenza A(H1N2) virus with a novel 7:1 genetic constellation was identified in a 68-year-old female patient with suspected pneumonia. The virus harboured A(H3N2) neuraminidase and remaining genes from A(H1N1)pdm09. The patient recovered after severe illness. No additional cases have been detected. This is the second identified A(H1N2) seasonal reassortant in a human in Europe within 1 year; a previous case was detected in the Netherlands in March 2018.

Low 2018/19 vaccine effectiveness against influenza A(H3N2) among 15-64-year-olds in Europe: exploration by birth cohort.

IntroductionInfluenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE).AimThe I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort.MethodsWe measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0-14, 15-64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32-54-year-olds (1964-86) sharing potential childhood imprinting to serine at haemagglutinin position 159.ResultsInfluenza A(H3N2) VE among all ages was -1% (95% confidence interval (CI): -24 to 18) and 46% (95% CI: 8-68), -26% (95% CI: -66 to 4) and 20% (95% CI: -20 to 46) among 0-14, 15-64 and ≥ 65-year-olds, respectively. Among 15-64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: -34 to 50) and -74% (95% CI: -259 to 16), respectively. VE was -18% (95% CI: -140 to 41), -53% (95% CI: -131 to -2) and -12% (95% CI: -74 to 28) among 15-31-year-olds (1987-2003), 32-54-year-olds (1964-86) and 55-64-year-olds (1954-63), respectively.DiscussionThe lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964-86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15-64-year-olds and the public health impact of the I-REV hypothesis warrant further study.