Whole-Genome Sequencing as Tool for Investigating International Tuberculosis Outbreaks: A Systematic Review

Background: Whole-genome sequencing (WGS) can support the investigation of tuberculosis (TB) outbreaks. The technique has been applied to estimate the timing and directionality of transmission and to exclude cases from an investigation. This review assesses how WGS was applied in international outbreak investigations and discusses the advantages and challenges of the application of WGS.Methods: Databases were searched for reports on international TB outbreak investigations. Information was extracted on: Why was WGS applied?; How was WGS applied?; Organizational issues; WGS methodology; What was learned/what were the implications of the WGS investigation?; and challenges and lessons learned.Results: Three studies reporting on international outbreak investigations were identified. Retrospective WGS sequencing was performed in all studies and prospective typing in two to study TB transmission. In one study, WGS data were produced centrally (i.e., in one laboratory) and analysis was done centrally. In two studies, WGS data production was done in a decentralized manner, and analysis was centralized in one laboratory. Three groups of professionals were involved in the international outbreak investigation: public health authorities, laboratory experts, and clinicians. The reported WGS methodology applied differed between the studies in some aspects, e.g., sequencing platform; quality measures, percentage of the reference genome covered, and the mean genomic coverage; analysis, use of a reference genome or de novo assembly; and software used for alignment and analysis. In all three studies, in-house scripts were used for variance calling, and the single nucleotide polymorphism (SNP) approach was used for analysis. All outbreak investigation reports stated that WGS refuted suspected transmission events and provided supporting evidence for epidemiological data. Several challenges were reported of which most were not related to WGS. The only challenge related to WGS was the timeframe of getting WGS data if WGS is not routinely performed.Conclusions: WGS was considered a useful addition in international TB outbreak investigations. Further standardization of the WGS methodology and good structures for international collaboration and coordination are needed to take full advantage of this new technology. Whether the use of WGS results in earlier detection of cases and thus limits transmission still needs to be determined

Influenza returns with a season dominated by clade 3C.2a1b.2a.2 A(H3N2) viruses, WHO European Region, 2021/22

In the WHO European Region, COVID-19 non-pharmaceutical interventions continued slowing influenza circulation in the 2021/22 season, with reduced characterisation data. A(H3) predominated and, in some countries, co-circulated with A(H1)pdm09 and B/Victoria viruses. No B/Yamagata virus detections were confirmed. Substantial proportions of characterised circulating virus subtypes or lineages differed antigenically from their respective northern hemisphere vaccine components. Appropriate levels of influenza virus characterisations should be maintained until the season end and in future seasons, when surveillance is adapted to integrate SARS-CoV-2.ECDC and WHO internal funds.S

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (</p

Molecular and genomic typing for tuberculosis surveillance: A survey study in 26 European countries

Background Molecular typing and whole genome sequencing (WGS) information is used for (inter-) national outbreak investigations. To assist the implementation of these techniques for tuberculosis (TB) surveillance and outbreak investigations at European level there is a need for inter-country collaboration and standardization. This demands more information on molecular typing practices and capabilities of individual countries. We aimed to review the use of molecular/genomic typing for TB surveillance in European Union and European Economic Area countries in 2016; assess its public health value; and collect experiences on typing data use for cross-border cluster investigations. Method A web-based questionnaire was provided to all TB National Focal Points. The questionnaire consisted of three parts: i) Use and integration of molecular and genomic typing data into TB surveillance; ii) Cross-border cluster investigation and international collaboration, and iii) Perception and evaluation of public health benefits of molecular and genomic typing for TB surveillance. Results Of 26 responding countries, 20 used molecular typing for TB surveillance, including nine applying WGS. The level of integration into the national surveillance was heterogeneous. Among six countries not using typing for TB surveillance, more than half planned its implementation soon. Overall, most countries perceived an added public health value of molecular typing for TB control. Concerning international cluster investigations, countries had little experience and did not have standard protocols to exchange typing data. Conclusion Our study shows a wide use of molecular and genomic typing data for TB surveillance in EU/EEA countries and reveals that transition to WGS-based typing is ongoing or is considered in most countries. However, our results also show a high heterogeneity in the use and integration of typing data for TB surveillance. Standardization of typing data use for TB surveillance is needed and formal procedures should be developed to facilitate international collaboration.Peer Reviewe

Új Mycobacterium tuberculosis törzs okozta mikroepidémia budapesti hajléktalanokban = Microepidemy due to a newly identified and specific local Mycobacterium tuberculosis clade among Hungarian homeless patients with tuberculosis in Budapest

Retrospektív tanulmányunkban, amely 2002-ben regisztrált 66 budapesti hajléktalantól származó M. tuberculosis törzset ölel fel, egy helyi mikrojárványt igazoltunk Budapest legmagasabb tuberculosis-incidenciájú kerületében. A molekuláris genetikai vizsgálatok (IS 6110-RFLP DNS-ujjlenyomat, spoligotyping, mycobacterial interspred repetitive unit és katG-gyrA tipizálás) egy helyi eredetű, Budapest-specifikus M. tuberculosis törzs jelenlétét igazolták. Ugyancsak figyelemre méltó a világszerte elterjedt, virulens Beijing-törzs hiánya. Eredményeink arra utalnak, hogy a hajléktalanok között a tuberculosis kontrolljára nagyobb figyelmet kell fordítani, és a megelőzés területén komolyabb lépésekre van szükség. In a retrospective study that included 66 homeless tuberculosis patients a local microepidemy was identified in the VIIIth district of Budapest with the highest tuberculosis incidence of the capital. Further molecular genetic characterization by IS6110 fingerprinting, spoligotyping and mycobacterial interspred repetitive unit (MIRU) typing has shown that the observed microepidemy was due to a locally emerged, Budapest-specific lineage. The absence of infections with the more virulent Beijing genotype is also noteworthy. The findings indicate that tuberculosis control and prevention steps among the homeless need to be strengthened in Hungary

The epidemiology of invasive meningococcal disease in EU/EEA countries, 2004–2014.

International audienceBackground: Invasive meningococcal disease (IMD) is a major cause of bacterial meningitis and septi-caemia although infection by some serogroups may be prevented through vaccination. We aimed to describe the epidemiology of IMD in EU/EEA countries during 2004-2014 to monitor serogroup-and age-specific trends, and compare country trends by the period of meningococcal C conjugate (MCC) vaccine introduction.Methods: We analysed IMD surveillance data by age, gender, serogroup, country and outcome. We estimated the percentage change in annual notification rate (NR), using linear regression analysis of the log of the annual NR. We grouped countries by the year they introduced MCC vaccination into their routine immunisation programmes. Results: The overall NR was 0.9/100 000 population, and decreased 6.6% (95%CI: À8.0%;À5.1%) annually. Infants had the highest NR (16.0/100 000), and there were decreasing trends in all age groups <50 years. Serogroup B (SgB) caused 74% of all cases, and the majority of cases in all age groups. There were decreasing trends in SgB and serogroup C (SgC) and an increasing trend in serogroup Y. Countries that introduced MCC vaccination before, and between 2004 and 2014, had decreasing trends in NR of SgC, but not countries without routine MCC vaccination.Conclusions: Our findings support evidence that routine MCC vaccination was the driving force behind the decreasing SgC trend. Vaccinating against SgB in the first year of life could help reduce the burden of IMD due to this serogroup. Changing serogroup-specific NR trends highlight the need for high-quality surveillance data to accurately assess the changing epidemiology of IMD, the effectiveness and impact of implemented vaccines, and the need for future vaccines