Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study.

BACKGROUND: Regular quality-assured whole-genome sequencing linked to antimicrobial resistance (AMR) and patient metadata is imperative to elucidate the shifting gonorrhoea epidemiology, both nationally and internationally. We aimed to examine the gonococcal population in the European Economic Area (EEA) in 2020, elucidate emerging and disappearing gonococcal lineages associated with AMR and patient metadata, compare with 2013 and 2018 whole-genome sequencing data, and explain changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: In this retrospective genomic surveillance study, we analysed consecutive gonococcal isolates that were collected in EEA countries through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) in 2020, and made comparisons with Euro-GASP data from 2013 and 2018. All isolates had linked AMR data (based on minimum inhibitory concentration determination) and patient metadata. We performed whole-genome sequencing and molecular typing and AMR determinants were derived from quality-checked whole-genome sequencing data. Links between genomic lineages, AMR, and patient metadata were examined. FINDINGS: 1932 gonococcal isolates collected in 2020 in 21 EEA countries were included. The majority (81·2%, 147 of 181 isolates) of azithromycin resistance (present in 9·4%, 181 of 1932) was explained by the continued expansion of the Neisseria gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) clonal complexes (CCs) 63, 168, and 213 (with mtrD/mtrR promoter mosaic 2) and the novel NG-STAR CC1031 (semi-mosaic mtrD variant 13), associated with men who have sex with men and anorectal or oropharyngeal infections. The declining cefixime resistance (0·5%, nine of 1932) and negligible ceftriaxone resistance (0·1%, one of 1932) was largely because of the progressive disappearance of NG-STAR CC90 (with mosaic penA allele), which was predominant in 2013. No known resistance determinants for novel antimicrobials (zoliflodacin, gepotidacin, and lefamulin) were found. INTERPRETATION: Azithromycin-resistant clones, mainly with mtrD mosaic or semi-mosaic variants, appear to be stabilising at a relatively high level in the EEA. This mostly low-level azithromycin resistance might threaten the recommended ceftriaxone-azithromycin therapy, but the negligible ceftriaxone resistance is encouraging. The decreased genomic population diversity and increased clonality could be explained in part by the COVID-19 pandemic resulting in lower importation of novel strains into Europe. FUNDING: European Centre for Disease Prevention and Control and Örebro University Hospital.

Tracing the adaptive evolution of SARS-CoV-2 during vaccine roll-out in Norway.

Vaccination against SARS-CoV-2 has greatly mitigated the impact of the COVID-19 pandemic. However, concerns have been raised about the degree to which vaccination might drive the emergence and selection of immune escape mutations that will hamper the efficacy of the vaccines. In this study, we investigate whether vaccination impacted the micro-scale adaptive evolution of SARS-CoV-2 in the Oslo region of Norway, during the first nine months of 2021, a period in which the population went from near-zero to almost 90 per cent vaccine coverage in the population over 50 years old. Weekly aggregated data stratified by age on vaccine uptake and number of SARS-CoV-2 cases in the area were obtained from the National Immunization Registry and the Norwegian Surveillance System for Communicable Diseases, respectively. A total of 6,438 virus sequences (7.5 per cent of the registered cases) along with metadata were available. We used a causal-driven approach to investigate the relationship between vaccination progress and changes in the frequency of 362 mutations present in at least ten samples, conditioned on the emergence of new lineages, time, and population vaccination coverage. After validating our approach, we identified 21 positive and 12 negative connections between vaccination progress and mutation prevalence, and most of them were outside the Spike protein. We observed a tendency for the mutations that we identified as positively connected with vaccination to decrease as the vaccinated population increased. After modelling the fitness of different competing mutations in a population, we found that our observations could be explained by a clonal interference phenomenon in which high fitness mutations would be outcompeted by the emergence or introduction of other high-fitness mutations.

Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative.

This review details recent findings from the Global Meningococcal Initiative's (GMI) recent meeting on the surveillance and control strategies for invasive meningococcal disease in the Middle East. The nature of case reporting and notification varies across the region, with many countries using bacterial meningitis as an IMD case definition in lieu of meningitis and septicaemia. This may overlook a significant burden associated with IMD leading to underreporting or misreporting of the disease. Based on these current definitions, IMD reported incidence remains low across the region, with historical outbreaks mainly occurring due to the Hajj and Umrah mass gatherings. The use of case confirmation techniques also varies in Middle Eastern countries. While typical microbiological techniques, such as culture and Gram staining, are widely used for characterisation, polymerase chain reaction (PCR) testing is utilised in a small number of countries. PCR testing may be inaccessible for several reasons including sample transportation, cost, or a lack of laboratory expertise. These barriers, not exclusive to PCR use, may impact surveillance systems more broadly. Another concern throughout the region is potentially widespread ciprofloxacin resistance since its use for chemoprophylaxis remains high in many countries.

Antibodies against Neisseria meningitidis serogroups A, C, W and Y in serum and saliva of Norwegian adolescents.

INTRODUCTION: The incidence of invasive meningococcal disease (IMD) among Norwegian 16-19-year-olds was 1-7/100,000 in the decade before the COVID-19 pandemic, with serogroup Y (MenY) dominance. In contrast to many other European countries, meningococcal vaccines are not part of the national immunisation program (NIP) in Norway. This cross-sectional study aimed to measure the degree of natural immunity against Neisseria meningitidis among adolescents in Norway to evaluate the need for introducing tetravalent meningococcal conjugate vaccine (MCV4) in the NIP. MATERIALS AND METHODS: Serum and saliva samples were collected from students in upper and lower secondary schools in Norway in 2018. Samples were analysed for meningococcal capsular polysaccharide (PS)-specific antibodies using a bead-based multiplex immunoassay. PS-specific antibody levels were linked to data on meningococcal carriage, vaccination status and risk factors for carriage (assessed with questionnaire) and analysed by linear regression of log transformed concentrations. A subset of samples from unvaccinated individuals was analysed for serum bactericidal antibodies (SBA). RESULTS: A total of 1344 participants, median age 16 years (range 12-24), were included in the study. Overall, 60.9% of the participants were female and 1137 (84.6%) were not vaccinated with MCV4. PS-specific antibody concentrations in serum and saliva were low among unvaccinated individuals for all serogroups and only 6.7-20.0% of the subpopulation with high PS-specific antibodies assessed with SBA had protective levels. Unvaccinated MenY carriers had higher levels of MenY anti-PS IgG in serum and IgA in saliva than those not carrying MenY. Use of Swedish snus was associated with lower anti-PS IgG levels in serum and waterpipe use with lower anti-PS IgG levels in saliva. CONCLUSION: Unvaccinated adolescents in Norway have a low degree of natural immunity against the serogroups of N. meningitidis predominating among cases of IMD in this age group. Therefore, introduction of MCV4 for adolescents in the NIP is recommended.

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008-2020.

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.

Invasive meningococcal disease in Norway in the two decades before the COVID-19 pandemic.

OBJECTIVES: Disease caused by the bacterium Neisseria meningitidis remains a worldwide public health challenge, despite the steadily decreasing incidence in Western countries. The objective of this study was to explore the epidemiology of invasive meningococcal disease in Norway over the last two decades. DESIGN: All isolates sent to the National Reference Laboratory from patients with invasive meningococcal disease between the years 2000 and 2019 were analyzed using whole genome sequencing (total: 625). RESULTS: A five-fold decrease in case numbers occurred over this period, and the situation has gone from being dominated by serogroup B to one where serogroups Y and W are more prevalent. Concurrently, the mean age at infection has increased from 18 to 33 years. Among the 350 serogroup B isolates, 87% were an exact match or cross-reactive with one or both the currently available serogroup B vaccines, but the proportion decreased in the past decade. Core genome analyses revealed a high variation in the number of allelic differences accumulated in epidemiologically linked isolates to the point that near-identical isolates were found several years apart. CONCLUSION: Allelic distance is an imprecise metric for the degree of epidemiologic linkage between isolates in N. meningitidis.

Genetic, Functional, and Immunogenic Analyses of the O-Linked Protein Glycosylation System in Neisseria meningitidis Serogroup A ST-7 Isolates.

Neisseria meningitidis exhibits a general O-linked protein glycosylation system in which pili and other extracytoplasmic proteins are glycosylated. To investigate glycan antigenicity in humans and the significance of high glycan diversity on immune escape mechanisms, we exploited serogroup A meningococcal strains and serum samples obtained from laboratory-confirmed Ethiopian patients with meningococcal disease. The 37 meningococcal isolates were sequenced, and their protein glycosylation (pgl) genotypes and protein glycosylation phenotypes were investigated in detail. An insertion sequence (IS1655) element in pglH reduced glycan variability in the majority of isolates, while phase variation strengthened glycan variability and microheterogeneity. Homologous recombination events within the pgl genes were identified in eight of the 37 isolates, and the phenotypic consequences ranged from none detected to altered glycoforms in two of the isolates in which the whole pgl locus was exchanged. Immunoblotting of sera against a complete panel of glycan-expressing mutant strains demonstrated that most of these patient sera had IgG antibodies against various neisserial protein glycan antigens. Furthermore, using a bactericidal assay comparing a wild-type meningococcal A strain and a glycosylation-null variant strain, we showed that these protein glycan antigens interfere with bactericidal killing by antibodies in patient sera. Altogether, we were largely able to link pgl genotype with glycosylation phenotype. Our study reveals that protein glycans seem to contribute to the ability of N. meningitidis to resist the bactericidal activity of human serum, possibly by masking protein epitopes important for bactericidal killing and thus protection against meningococcal disease. IMPORTANCE Bacterial meningitis is a serious global health problem, and one of the major causative organisms is Neisseria meningitidis. Extensive variability in protein glycan structure and antigenicity is due to phase variation of protein glycosylation genes and polymorphic gene content and function. The exact role(s) of glycosylation in Neisseria remains to be determined, but increasing evidence, supported by this study, suggests that glycan variability can be a strategy to escape the human immune system. The complexity of the O-linked protein glycosylation system requires further studies to fully comprehend how these bacteria utilize variation in pgl genes to produce such high glycoform diversity and to evade the human immune response.

Meningococcal disease in North America: Updates from the Global Meningococcal Initiative.

This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of ß-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI.

Naturally occurring Neisseria gonorrhoeae can have large deletions in housekeeping gene abcZ, making them untypable with multilocus sequence typing.

The abcZ gene is an essential housekeeping gene in all the Neisseria species. It is one of the seven genes used for multilocus sequence typing (MLST) this genus. It encodes the cytosolic component of an ATP-binding cassette (ABC) transporter complex of unknown function. We report here the finding of a strain of Neisseria gonorrhoeae with a 485 base pair deletion in the 5' region of the abcZ gene that truncates the protein product from 636 amino acids to 89 amino acids. A second open reading frame (ORF), encoding the latter 388 amino acids of the abcZ gene, was predicted downstream. The deletion will affect MLST profiling; interrogation of genomic sequences from PubMLST revealed that this isolate is not an anomaly. Deletions in abcZ were identified in 256 Neisseria genomes, roughly 0.6% of isolates. Furthermore, these deletions could leave the abcZ gene in a pseudogenized state. Our strain, isolated from a patient with symptoms of gonorrheal infection, nevertheless behaved normal in terms of growth and in vitro phenotypic properties.

Surveillance and control of meningococcal disease in the COVID-19 era: A Global Meningococcal Initiative review.

This review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes.

The impact of global lineage dynamics, border restrictions, and emergence of the B.1.1.7 lineage on the SARS-CoV-2 epidemic in Norway.

As the COVID-19 pandemic swept through an immunologically naïve human population, academics and public health professionals scrambled to establish methods and platforms for genomic surveillance and data sharing. This offered a rare opportunity to study the ecology and evolution of SARS-CoV-2 over the course of the ongoing pandemic. Here, we use population genetic and phylogenetic methodology to characterize the population dynamics of SARS-CoV-2 and reconstruct patterns of virus introductions and local transmission in Norway against this backdrop. The analyses demonstrated that the epidemic in Norway was largely import driven and characterized by the repeated introduction, establishment, and suppression of new transmission lineages. This pattern changed with the arrival of the B.1.1.7 lineage, which was able to establish a stable presence concomitant with the imposition of severe border restrictions.

Meningococcal Carriage among Household Contacts of Patients with Invasive Meningococcal Disease in Kathmandu, Nepal: A Longitudinal Study.

Because asymptomatic carriers are key source of transmission, information on meningococcal carriage in the community provides a scientific basis for appropriate preventive/control strategies. This longitudinal study (January 2017-December 2019) aimed to estimate carriage rate of meningococci among household contacts of meningococcal meningitis cases within Kathmandu Valley, Nepal. Throat swab samples were collected at first visit from each person in households, twice a month for up to 2 months and subsequently on a monthly basis for a further 4 months. Altogether, 1125 throat samples were processed by conventional culture for the identification of meningococci. To the best of our knowledge, this is the first longitudinal study on meningococcal carriage in Nepal. The meningococcal carriage rate among household contacts was 15%. All carriers were aged 19 years or older. There was no statistically significant gender difference. The duration of carriage was 60 days. Twenty of 36 isolates belonged to serogroup A, and 16 were non-serogroupable (NG). Serogroups isolated from the same individuals did not change within the follow-up period. All meningococcal isolates over the past 38 years in Nepal that have been reported in previous studies have belonged to serogroup A. The detection of NG meningococcal isolates in apparently healthy household contacts clearly indicates the importance of vigilance through surveillance and periodic in-depth studies.

The effect of recombination on the evolution of a population of Neisseria meningitidis.

Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.

Detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in Culture Negative Cerebrospinal Fluid Samples from Meningitis Patients Using a Multiplex Polymerase Chain Reaction in Nepal.

The rapid identification of bacteria causing meningitis is crucial as delays in the treatment increase mortality rate. Though considered as the gold standard for the laboratory diagnosis of bacterial meningitis, culture might give false negative results in a case of patients under antibiotics prior to lumbar puncture. This study aimed to detect Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae by a multiplex polymerase chain reaction (PCR) in culture-negative cerebrospinal fluid samples collected from clinically suspected meningitis cases attending different hospitals in Kathmandu, Nepal from January 2017 to December 2019. S. pneumoniae, N. meningitidis and H. influenzae were detected in 8.59% (33/384) of the specimens by PCR and 7.55% (29/384) of the specimens by culture. Correlation between culture and PCR of the same sample was good (Spearman's rho correlation coefficient = 0.932). However, the difference in positivity between culture and PCR was statistically not significant (p value > 0.05). In four specimens, culture could not detect any of the targeted bacteria whereas PCR could detect presence of H. influenzae. PCR increases the diagnostic yield for bacterial meningitis. PCR may be considered as an adjunctive test for establishing the cause of infection in culture negative clinically suspected meningitis cases.

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review.

Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.

Cost-effectiveness of meningococcal vaccination of Norwegian teenagers with a quadrivalent ACWY conjugate vaccine.

In Norway, the incidence of invasive meningococcal disease (IMD) is higher among 16-19-year-olds than in the general population. Most IMD cases among teenagers are caused by serogroup Y. Since 2011, one dose of meningococcal ACWY conjugate vaccine (MCV4) has been recommended for teenagers with out-of-pocket payment. The teenagers are usually vaccinated through the school health service at age 18. This study aimed to estimate costs and health gains of introducing MCV4 to Norwegian teenagers through the national immunization program (NIP). A Markov model was used to analyze the cost-effectiveness of universal MCV4 vaccination of either 15-year-olds or 18-years-olds. Occurrences of IMD were simulated from 15 until 23 years of age. Costs were estimated from a healthcare perspective. Sensitivity analyses evaluated the impact of vaccine price, vaccination uptake, IMD incidence and discount rate. Compared to today's practice of vaccinating 18-year-olds with out-of-pocket payment, introducing MCV4 to 15-year-olds in a NIP-setting, with 90% vaccine uptake and 50% rebate on vaccine price, prevented 3.2 hospitalizations, 0.20 sequelae and 0.47 deaths among 15-23-year-olds, annually. Total costs were reduced by €30,000 and 9.7 quality-adjusted life-years (QALYs) were gained per birth cohort. The probability of cost-effectiveness was 99.0%, assuming a willingness-to-pay threshold of €86,000/QALY for severe diseases in Norway. Cost-effectiveness was highly dependent on vaccine price. Vaccination of 18-year-olds in a NIP-setting was also cost-effective, but less than NIP-vaccination of 15-year-olds. Introduction of MCV4 to the 15-year-olds in the Norwegian NIP is likely to be cost-effective given a rebate on the vaccine price.

Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage.

The Neisseria gonorrhoeae multilocus sequence type (ST) 1901 is among the lineages most commonly associated with treatment failure. Here, we analyze a global collection of ST-1901 genomes to shed light on the emergence and spread of alleles associated with reduced susceptibility to extended-spectrum cephalosporins (ESCs). The genetic diversity of ST-1901 falls into a minor and a major clade, both of which were inferred to have originated in East Asia. The dispersal of the major clade from Asia happened in two separate waves expanding from ∼1987 and 1996, respectively. Both waves first reached North America, and from there spread to Europe and Oceania, with multiple secondary reintroductions to Asia. The ancestor of the second wave acquired the penA 34.001 allele, which significantly reduces susceptibility to ESCs. Our results suggest that the acquisition of this allele granted the second wave a fitness advantage at a time when ESCs became the key drug class used to treat gonorrhea. Following its establishment globally, the lineage has served as a reservoir for the repeated emergence of clones fully resistant to the ESC ceftriaxone, an essential drug for effective treatment of gonorrhea. We infer that the effective population sizes of both clades went into decline as treatment schemes shifted from fluoroquinolones via ESC monotherapy to dual therapy with ceftriaxone and azithromycin in Europe and the United States. Despite the inferred recent population size decline, the short evolutionary path from the penA 34.001 allele to alleles providing full ceftriaxone resistance is a cause of concern.

Sudden emergence of a Neisseria gonorrhoeae clade with reduced susceptibility to extended-spectrum cephalosporins, Norway.

Neisseria gonorrhoeae multilocus sequence type (ST)-7827 emerged in a dramatic fashion in Norway in the period 2016-2018. Here, we aim to shed light on the provenance and expansion of this ST. ST-7827 was found to be polyphyletic, but the majority of members belonged to a monophyletic clade we termed PopPUNK cluster 7827 (PC-7827). In Norway, both PC-7827 and ST-7827 isolates were almost exclusively isolated from men. Phylogeographical analyses demonstrated an Asian origin of the genogroup, with multiple inferred exports to Europe and the USA. The genogroup was uniformly resistant to fluoroquinolones, and associated with reduced susceptibility to both azithromycin and the extended-spectrum cephalosporins (ESCs) cefixime and ceftriaxone. From a genetic background including the penA allele 13.001, associated with reduced ESC susceptibility, we identified repeated events of acquisition of porB alleles associated with further reduction in ceftriaxone susceptibility. Transmission of the strain was significantly reduced in Norway in 2019, but our results indicate the existence of a recently established global reservoir. The worrisome drug-resistance profile and rapid emergence of PC-7827 calls for close monitoring of the situation.

Next generation rapid diagnostic tests for meningitis diagnosis.

Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the "Defeating Meningitis by 2030" roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs.