Disease Burden of Invasive Meningococcal Disease in the Netherlands Between June 1999 and June 2011: A Subjective Role for Serogroup and Clonal Complex.

BACKGROUND: Several countries consider the implementation of a meningococcal serogroup B vaccine for young children and/or serogroup C or ACWY conjugate vaccine for adolescents. Representative information on clinical course of invasive meningococcal disease (IMD) is useful to evaluate cost-effectiveness of vaccination. Information on the relation between infecting meningococcal clonal complex (CC), disease course and outcome of IMD is scarce. METHODS: A retrospective study using Dutch surveillance data on IMD from June 1999 to June 2011. Clinical information was retrieved from hospital records. The effect of age, comorbidity, clinical manifestation, serogroup, and CC on disease course and outcome was assessed in multivariable analyses. Meningococcal CCs were assessed by multilocus sequence typing. RESULTS: Clinical information was retrieved for 879 IMD cases: 48% of patients presented with meningitis, 17% with septic shock, and 22% with septic shock plus meningitis. Development of septic shock was not related to CC or serogroup. Median (interquartile range) duration of hospital admission was 10 (8-13) days. Intensive care unit admittance (38%) was higher for patients aged ≥10 years and patients with septic shock (P-values ≤.001). Case-fatality rate (8%) and development of sequelae (29%) was dependent on age and clinical manifestation (P-values ≤.001) and not affected by comorbidity, CC, or serogroup. CONCLUSIONS: IMD still coincides with a considerable disease burden and mortality. Disease course and outcome depend mainly on age and clinical manifestation and less on meningococcal CC or serogroup.

Influenza Infection and Acute Myocardial Infarction.

BACKGROUND: Acute respiratory infections can trigger acute myocardial infarction. We aimed to quantify the association between laboratory-confirmed influenza infection and acute myocardial infarction, particularly in patients with and without known coronary artery disease. METHODS: This observational, registry-based, self-controlled case series study evaluated the association between laboratory-confirmed influenza infection and occurrence of acute myocardial infarction. Laboratory records on respiratory virus polymerase chain reaction (PCR) testing from 16 laboratories across the Netherlands were linked to national mortality, hospitalization, medication, and administrative registries. Influenza infection was defined as a positive PCR test result. Acute myocardial infarction was defined as a registered diagnostic code for either acute myocardial infarction hospitalization or death. Using a self-controlled case series method, we then compared the incidence of acute myocardial infarction during the risk period (days 1 to 7 after influenza infection) versus the control period (1 year before and 51 weeks after the risk period). RESULTS: Between 2008 and 2019, we identified 158,777 PCR tests for influenza in the study population; 26,221 were positive for influenza, constituting 23,405 unique influenza illness episodes. A total of 406 episodes were identified with acute myocardial infarction occurring within 1 year before and 1 year after confirmed influenza infection and were included in analysis. Twenty-five cases of acute myocardial infarction occurred during the risk period versus 394 during the control period. The adjusted relative incidence of acute myocardial infarction during the risk period compared with the control period was 6.16 (95% confidence interval [CI], 4.11 to 9.24). The relative incidence of acute myocardial infarction in individuals without prior hospitalization for coronary artery disease was 16.60 (95% CI, 10.45 to 26.37) compared with 1.43 (95% CI, 0.53 to 3.84) for those with prior admission for coronary artery disease. CONCLUSIONS: Influenza infection was associated with an increased risk of acute myocardial infarction, especially in individuals without a prior hospitalization for coronary artery disease. (Funded by the Dutch Research Council [NWO].).

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19.

Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

Novel emm4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022.

Invasive group A streptococcal (iGAS) disease cases increased in the first half of 2022 in the Netherlands, with a remarkably high proportion of emm4 isolates. Whole-genome sequence analysis of 66 emm4 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 (M4NL22), which accounted for 85 % of emm4 iGAS cases in 2022. Surprisingly, we detected few isolates of the emm4 hypervirulent clone, which has replaced nearly all other emm4 in the USA and the UK. M4NL22 displayed genetic differences compared to other emm4 strains, although these were of unclear biological significance. In publicly available data, we identified a single Norwegian isolate belonging to M4NL22, which was sampled after the isolates from this study, possibly suggesting export of M4NL22 to Norway. In conclusion, our study identified a novel S. pyogenes emm4 lineage underlying an increase of iGAS disease in early 2022 in the Netherlands and the results have been promptly communicated to public health officials.

[Invasive group A streptococcal infections in the Netherlands]. / Invasieve groep A-streptokokkeninfecties in Nederland.

Group A streptococcal (GAS) infections are caused by the Gram-positive bacterium Streptococcus pyogenes. Infection can occur via droplet infection from the throat and via (in)direct contact with infected people. GAS can cause a wide variety of diseases, ranging from superficial skin infections, pharyngitis and scarlet fever, to serious invasive diseases such as puerperal sepsis, pneumonia, necrotising soft tissue infections (NSTI) (also known as necrotising fasciitis/myositis), meningitis and streptococcal toxic shock syndrome (STSS). In invasive GAS infections, the bacteria has penetrated into a sterile body compartment (such as the bloodstream, deep tissues, or the central nervous system). Invasive GAS infections are rare but serious, with high morbidity and mortality. Since March 2022, the National Institute for Public Health and the Environment (RIVM) reported a national increase in notifiable invasive GAS infections (NSTI, STSS and puerperal fever). Particularly NSTI has increased compared to the years before the SARS-CoV-2 pandemic. Remarkably, the proportion of children aged 0 to 5 years with invasive GAS-infections is higher in 2022 than in the previous years (12% compared to 4%). While seasonal peaks occur, the current elevation exceeds this variation. To promote early recognition and diagnosis of invasive GAS infections different clinical cases are presented.

In-depth Characterization of Vaccine Breakthrough Infections With SARS-CoV-2 Among Health Care Workers in a Dutch Academic Medical Center.

Severe acute respiratory syndrome coronavirus 2 infection after coronavirus disease 2019 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch health care workers ≥14 days after the final dose of vaccination with either BNT162b2, mRNA-1273, or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine-induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.

[Diphtheria: a 'forgotten' disease?] / Difterie: een 'vergeten' ziekte?

Respiratory diphtheria is an acute respiratory tract infection. The high mortality rates (5-10%) are related to airway obstruction and local and systemic effects of the diphtheria toxin. Vaccination against diphtheria has been available through the Dutch national vaccination programme since the 1950s. The disease has now become rare as a result of herd immunity by these vaccinations. As a consequence, the disease has largely been forgotten, which can result in it not being recognised and treated in time. In addition, diphtheria antitoxin is not always available. In this article, we are drawing attention to the need for immunisation. We also look back at how diphtheria prevention started in the Netherlands.

Molecular surveillance on Streptococcus pneumoniae carriage in non-elderly adults; little evidence for pneumococcal circulation independent from the reservoir in children.

Carriage of Streptococcus pneumoniae in adults is rarely detected by the gold standard culture method. With molecular tests of high sensitivity now available, we analysed upper respiratory tract samples collected during autumn/winter 2012/2013 from parents of PCV7-vaccinated infants and from childless adults, directly comparing culture and qPCR-based S. pneumoniae detection. As compared to the gold standard of testing nasopharyngeal swabs, qPCR-based analysis of oral samples significantly improved detection of pneumococcal carriage (5% versus 20%, p < 0.0001) with higher carriage rates in parents compared to childless adults (34% versus 7%; p < 0.001). Molecular methods also increased the number of serotype-carriage events detected with higher carriage frequencies of serotypes 3 and 7A/F and lower of serotypes 6C/D and 15A/B/C in parents compared to their infant children. We provide evidence that culture-based methods severely underestimate adult carriage rates and for the superiority of testing oral samples over nasopharyngeal swabs. The substantial circulation of pneumococci in parents is however, not representative for the entire adult population. While age-associated differences in serotype carriage suggests reservoirs outside infants as potential sources of vaccine-serotypes contributing to weakening of vaccine herd effects, we find no evidence for reservoirs in adults contributing to serotype replacement in carriage.