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This study reports an epidemiological assessment of laboratory-confirmed group A streptococcal meningitis cases in the Netherlands using more than 40 years of national bacteriological surveillance data. [ABSTRACT FROM AUTHOR]

Background: The Netherlands is one of the six European countries considered on track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous efforts have to be put into designing efficient case‐finding strategies, including the retrieval of previously diagnosed hepatitis C virus‐infected who are lost to follow‐up. Aims: To trace and treat all lost to follow‐up hepatitis C virus patients in the Utrecht region and create an efficient retrieval strategy that can be used in future (national) retrieval initiatives. Methods: Positive hepatitis C virus diagnostic tests (anti‐hepatitis C virus IgG or hepatitis C virus‐RNA) from the laboratory of all four hospitals and one central laboratory for primary care diagnostics in the province of Utrecht from 2001 to 2015 were linked to clinical records. Untreated patients with available contact information were deemed eligible for retrieval and invited for reevaluation with (virology) blood tests, fibroscan measurement and possible direct‐acting antiviral therapy. Main results: After screening all hepatitis C virus diagnostics, 1913 chronic hepatitis C virus‐infected were identified of which 14.1% (n = 269) were invited back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those who lived in the Utrecht province. Through renewed patient assessments, 42 chronic hepatitis C virus infections were re‐identified (76% with a history of intravenous drug use, 24% with Metavir F3‐F4). Until now, 59% has either scheduled or initiated direct‐acting antiviral therapy. Conclusion: The retrieval of previously diagnosed hepatitis C virus patients through screening of laboratory diagnostics from the past is feasible and should be pursued for further control and reduction of hepatitis C virus infection. Retrieval is most successful when performed regionally. Lay summary: To completely eliminate chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed and also previously diagnosed but lost to follow‐up (LFU) HCV patients have to be brought (back) into care for therapy. Retrieval of LFU HCV patients through screening of laboratory diagnostics from the past is feasible and most successful when performed regionally. [ABSTRACT FROM AUTHOR]

In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004-June 2006) with those after PCV7 introduction (June 2008-June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ≈25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non-PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50-64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non-PCV7 serotype IPD. [ABSTRACT FROM AUTHOR]

Several case studies have reported on neurological complications caused by a primary Epstein-Barr virus (EBV) infection. We aimed to investigate the viral loads and the clinical and inflammatory characteristics of this disease entity. We evaluated all 84 cases in which the EBV polymerase chain reaction test (PCR) was requested on cerebrospinal fluid (CSF) for the period 2003-2008. Fourteen patients with proven neuroborreliosis served as the control group. Nine patients were diagnosed with a primary EBV infection and neurological symptoms (median age 36 y; 4 male). Viral DNA copies in CSF were detected by PCR in 7 of 9 patients. The presenting symptoms were meningeal signs, epileptic insults, polyradiculomyelitis, polyradiculitis, and/or sudden cognitive disorders. All EBV cases had a pleocytosis with significantly increased mononuclear leukocytes as compared to the neuroborreliosis group (median 99% interquartile range (96-100%) versus 90% (86-97%). In cases with a primary EBV infection, viral loads ranged from 43 to 3202 copies/ml in CSF and from 61 to 15,595 copies/ml in serum. Seventy-eight percent of the cases had a positive PCR on CSF. This study provides criteria for diagnosing neurological disease during primary EBV infection. Primary EBV infections in immune competent persons can cause a broad range of neurological symptoms, with lymphocytic and monocytic inflammation both in blood and CSF. [ABSTRACT FROM AUTHOR]

Since 2022, many countries have reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in Streptococcus pyogenes carriage rates or emergence of strains with potentially altered virulence, such as emm 1 variants M1 UK and M1 DK , contributed to the 2022/2023 surge in the Netherlands. We determined emm (sub)type distribution for 2,698 invasive and 351 S . pyogenes carriage isolates collected between January 2009 and March 2023. Genetic evolution of emm 1 was analyzed by whole-genome sequencing of 497 emm 1 isolates. The nationwide iGAS upsurge coincided with a sharp increase of emm 1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher's exact test, P < 0.0001). M1 UK became dominant among invasive emm 1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1 UK clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of emm 1 isolates. S. pyogenes carriage rates and emm 1 proportions in carriage isolates remained stable during this surge, and the expansion of M1 UK in iGAS was not reflected in carriage isolates. During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1 UK clades was observed among invasive isolates, but not carriage isolates, suggesting increased virulence and fitness of M1 UK compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.IMPORTANCEThis study describes the molecular epidemiology of invasive group A streptococcal (iGAS) infections in the Netherlands based on >3,000 Streptococcus pyogenes isolates from both asymptomatic carriers and iGAS patients collected before, during, and after the COVID-19 pandemic period (2009-2023) and is the first to assess whether changes in carriage rates or carried emm types contributed to the alarming post-COVID-19 upsurge in iGAS infections. We show that the 2022/2023 iGAS surge coincided with a sharp increase of emm 1, particularly the toxicogenic M1 UK variant, in invasive isolates, but not in carriage isolates. These findings suggest that increased virulence and fitness of M1 UK likely contributes to an increased dissemination between hosts. The emergence of a more virulent and fit lineage has important implications for iGAS control interventions such as antibiotic prophylaxis for close contacts of iGAS patients and calls for a reappraisal of iGAS control interventions and guidelines., Competing Interests: N.M.V.S. reports fee for service and presentations from MSD and GSK, grants from the Dutch Health Council (ZonMW; all directly paid to the institution), contract research with Argenx (unrelated to this work), a patent on vaccine development against S. pyogenes (licensee: University of California San Diego, inventors Nina van Sorge and Victor Nizet; licensed by Vaxcyte; personal revenue), and participation in the science advisory board of the ItsME foundation (no honorarium; https://itsme-foundation.com/en/) and Rapua te me ngaro ka tau, a project facilitating Strep A vaccine development for Aotearoa New Zealand (honorarium paid directly to the institution). M.A.V.H. reports grants or contracts with Pfizer (RSV prevention uptake study) and consulting fee from Pfizer on RSV vaccination (both unrelated to this work). Other authors have nothing to disclose.

Invasive group A streptococcal (iGAS) disease cases increased in the first half of 2022 in the Netherlands, with a remarkably high proportion of emm 4 isolates. Whole-genome sequence analysis of 66 emm 4 isolates, 40 isolates from the pre-coronavirus disease 2019 (COVID-19) pandemic period 2009-2019 and 26 contemporary isolates from 2022, identified a novel Streptococcus pyogenes lineage (M4 NL22 ), which accounted for 85 % of emm 4 iGAS cases in 2022. Surprisingly, we detected few isolates of the emm 4 hypervirulent clone, which has replaced nearly all other emm 4 in the USA and the UK. M4 NL22 displayed genetic differences compared to other emm 4 strains, although these were of unclear biological significance. In publicly available data, we identified a single Norwegian isolate belonging to M4 NL22 , which was sampled after the isolates from this study, possibly suggesting export of M4 NL22 to Norway. In conclusion, our study identified a novel S. pyogenes emm 4 lineage underlying an increase of iGAS disease in early 2022 in the Netherlands and the results have been promptly communicated to public health officials.