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  • 1
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    Online Resource
    mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity
    American Association for the Advancement of Science (AAAS) ; 2014
    In:  Science Vol. 345, No. 6204 ( 2014-09-26)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 345, No. 6204 ( 2014-09-26)
    Abstract: Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD + ) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1–Akt–HIF-1α (hypoxia-inducible factor–1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate–activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell–specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt–mTOR–HIF-1α pathway represents the metabolic basis of trained immunity.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1250684
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2014
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  • 2
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    Higher Neisseria gonorrhoeae bacterial load in coinfections with Chlamydia trachomatis compared with Neisseria gonorrhoeae single infections does not lead to more symptoms
    BMJ ; 2024
    In:  Sexually Transmitted Infections Vol. 100, No. 2 ( 2024-03), p. 127-128
    Details
    In: Sexually Transmitted Infections, BMJ, Vol. 100, No. 2 ( 2024-03), p. 127-128
    Type of Medium: Online Resource
    ISSN: 1368-4973 , 1472-3263
    URL: Article
    DOI: 10.1136/sextrans-2023-055977
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2027968-1
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  • 3
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    Linked nosocomial COVID-19 outbreak in three facilities for people with intellectual and developmental disabilities due to SARS-CoV-2 variant B.1.1.519 with spike mutation T478K in the Netherlands
    Springer Science and Business Media LLC ; 2022
    In:  BMC Infectious Diseases Vol. 22, No. 1 ( 2022-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: Individuals with intellectual and developmental disabilities (IDD) living in congregated settings have increased risk of COVID-19 infection and mortality. Little is known about variant B.1.1.519 with spike mutation T478K, dominant in Mexico. We describe a linked SARS-CoV-2 B.1.1.519 outbreak in three IDD facilities in the Netherlands. Methods Following notification of the index, subsequent cases were identified through serial PCR group testing. Positive specimens were submitted for whole-genome-sequencing. Clinical information was gathered through interviews with staff members of the three facilities. Results Attack rate (AR) in clients of the index facility was 92% (23/25), total AR in clients 45% (33/73) and in staff members 24% (8/34). 55% (18/33) of client cases were asymptomatic, versus 25% (2/8) of staff members. Five client cases (15%) were hospitalized, two died (6%). Sequencing yielded the same specific B.1.1.519 genotype in all three facilities. No significant difference in median viral load was established comparing the B.1.1.519 variant with other circulating variants. The index of the linked outbreak reported no travel history or link to suspected or confirmed cases suggesting regional surveillance. Observed peak regional prevalence of B.1.1.519 during the outbreak supports this. Conclusion AR, morbidity and mortality prior to control measures taking effect were high, probably related to the specific characteristics of the IDD setting and its clients. We assessed no evidence for intrinsic contributing properties of variant B.1.1.519. Our study argues for enhanced infection prevention protocols in the IDD setting, and prioritization of this group for vaccination against COVID-19.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-022-07121-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 4
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    Increased transmissibility of SARS-CoV-2 alpha variant (B.1.1.7) in children: three large primary school outbreaks revealed by whole genome sequencing in the Netherlands
    Springer Science and Business Media LLC ; 2022
    In:  BMC Infectious Diseases Vol. 22, No. 1 ( 2022-08-29)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-08-29)
    Abstract: Variant of concern (VOC) SARS-CoV-2 alpha variant (B.1.1.7) was the dominant strain in the Netherlands between March 2021–June 2021. We describe three primary school outbreaks due to the alpha variant using whole genome sequencing with evidence of large-scale transmission among children, teachers and their household contacts. Method All outbreaks described were investigated by the South Limburg Public Health Service, the Netherlands. A case was defined as an individual with a real-time polymerase chain reaction test or antigen test positive for SARS-CoV-2. Whole genome sequencing was performed on random samples from at least one child and one teacher of each affected class. Results Peak attack rates in classes were 53%, 33% and 39%, respectively. Specific genotypes were identified for each school across a majority of affected classes. Attack rates were high among staff members, likely to promote staff-to-children transmission. Cases in some classes were limited to children, indicating child-to-child transmission. At 39%, the secondary attack rate (SAR) in household contacts of infected children was remarkably high, similar to SAR in household contacts of staff members (42%). SAR of household contacts of asymptomatic children was only 9%. Conclusion Our findings suggest increased transmissibility of the alpha variant in children compared to preceding non-VOC variants, consistent with a substantial rise in the incidence of cases observed in primary schools and children aged 5–12 since the alpha variant became dominant in March 2021. Lack of mandatory masking, insufficient ventilation and lack of physical distancing also probably contributed to the school outbreaks. The rise of the delta variant (B.1.617.2) since July 2021 which is estimated to be 55% more transmissible than the alpha variant, provides additional urgency to adequate infection prevention in school settings.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-022-07623-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041550-3
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  • 5
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    Table_5.XLSX
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-11-24)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-11-24)
    Abstract: Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Vaxzevria or Jcovden being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Furthermore, the majority of adaptive mutations were concentrated in the N-terminal domain of the Spike protein, highlighting its role in immune evasion. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant were associated with increased viral loads compared to those caused by the Alpha variant. In addition, we investigated the role of the Omicron variant in causing breakthrough infections by analyzing 135 samples that were randomly selected for genomic surveillance during the transition period from Delta to Omicron. We found that the proportion of Omicron vs. Delta infections was significantly higher in individuals who received a booster vaccine compared to both unvaccinated and fully vaccinated individuals. Altogether, these results indicate that the emergence of the Delta variant and in particular Omicron has lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.1027271
    DOI: 10.3389/fmicb.2022.1027271.s001
    DOI: 10.3389/fmicb.2022.1027271.s002
    DOI: 10.3389/fmicb.2022.1027271.s003
    DOI: 10.3389/fmicb.2022.1027271.s004
    DOI: 10.3389/fmicb.2022.1027271.s005
    DOI: 10.3389/fmicb.2022.1027271.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 6
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    Video_1.MOV
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 14 ( 2023-5-18)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-5-18)
    Abstract: In an attempt to control the spread of SARS-CoV-2, many governments decided to close public venues including bars, restaurants, and nightclubs during the pandemic, making it difficult to study how transmission occurs in these environments. In this study, we were able to gain insight into the transmission dynamics of SARS-CoV-2 in 16 venues in the city of Maastricht using a combination of epidemiological and whole-genome sequencing (WGS) data during a period of 2 weeks in 2021, when bars, restaurants, and nightclubs were temporarily reopened in the Netherlands. This led to a subsequent rise of SARS-CoV-2 cases in the community following the reopening. Methods WGS was performed on samples from 154/348 of selected cases and combined with epidemiological investigation (e.g., contact tracing and linking cases to specific venues) to identify SARS-CoV-2 transmission clusters. In addition, genomic surveillance data were used to investigate spillover of outbreak-associated genotypes into the community. Results Clustering was observed in 129/136 (95%) successfully genotyped samples. We established that most cases were linked to venues with dancing facilities and that specific genotypes of the Delta variant were more frequently spread within and from these venues compared to venues without dancing facilities. In addition, we show indications of spillover of certain genotypes from the bar and restaurant industry into the community, with the number of hospital admissions increasing in the weeks following peak cases in the community. Conclusion Lifting restrictions on bar and restaurant industry venues with a corona entree ticket in a largely unvaccinated population led to a surge in COVID-19 cases and promoted the spread of new (sub)variants. Nightclubs were identified as potential super-spreading locations.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2023.1183877
    DOI: 10.3389/fmicb.2023.1183877.s001
    DOI: 10.3389/fmicb.2023.1183877.s002
    DOI: 10.3389/fmicb.2023.1183877.s003
    DOI: 10.3389/fmicb.2023.1183877.s004
    DOI: 10.3389/fmicb.2023.1183877.s005
    DOI: 10.3389/fmicb.2023.1183877.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 7
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    Infections with the SARS-CoV-2 Delta variant exhibit fourfold increased viral loads in the upper airways compared to Alpha or non-variants of concern
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-08-17)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-08-17)
    Abstract: There has been a growing body of evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) shows enhanced transmissibility and increased viral loads compared to other variants. A recent study has even suggested that respiratory samples from people infected with the Delta variant can harbor up to 1000 times higher viral loads compared to samples with variants that are more closely related to the original Wuhan strain, although the sample size of this study (n = 125) was very limited. Here, we have compared the viral load in 16,185 samples that were obtained in periods during which non-VOC, the Alpha (B.1.1.7) or Delta variant (B.1.617.2) were dominant as evidenced by genomic surveillance. We found that the Delta variant contained about fourfold higher viral loads across all age groups compared to the non-VOC or Alpha variants, which is significantly lower than reported earlier. Interestingly, the increased viral load for the Delta variant seemed to be age-dependent, regardless of sex, as the viral load was about 14-fold higher for Delta compared to the non-VOC or Alpha variant in age group 0–20 years and fourfold higher in age group 21–40 years, while there was no difference in viral load between variants in age groups 41–60 and 61+ years, most likely as a consequence of a higher degree of vaccination in the older age groups.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-18279-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 8
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    Men and Women Have Similar Neisseria gonorrhoeae Bacterial Loads: a Comparison of Three Anatomical Sites
    American Society for Microbiology ; 2020
    In:  Journal of Clinical Microbiology Vol. 58, No. 11 ( 2020-10-21)
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 58, No. 11 ( 2020-10-21)
    Abstract: Neisseria gonorrhoeae is a common bacterial sexually transmitted infection (STI). Currently, there are limited data on the bacterial load in both men and women and on both genital and extragenital sites. Therefore, we quantified N. gonorrhoeae bacterial loads in a large population of women, heterosexual men, and men who have sex with men (MSM) at three different anatomical sites. N. gonorrhoeae -positive samples ( n  = 1265) of STI clinic consultations ( n  = 944) were tested for N. gonorrhoeae with the Roche Cobas 4800 system, and quantification cycle ( Cq ) values were used as an inversely proportional measure for N. gonorrhoeae bacterial load after interpolation from a standard curve. Bacterial loads were compared between sample materials and sexes using t tests. The following mean N. gonorrhoeae loads were observed: urine, 4.5 ± 1.0 log 10 CFU/ml; vaginal swabs, 4.3 ± 1.1 log 10 CFU/ml; anorectal swabs (women), 4.0 ± 1.2 log 10 CFU/ml; anorectal swabs (men), 4.5 ± 1.3 log 10 CFU/ml; oropharyngeal swabs (women), 2.8 ± 0.9 log 10 CFU/ml; and oropharyngeal swabs (men), 3.2 ± 1.0 log 10 CFU/ml. Oropharyngeal swabs had a significantly lower N. gonorrhoeae load ( P 〈 0.001) than genital and anorectal samples. Loads did not differ between men and women. This is the first study that determined N. gonorrhoeae load in both women and men at three anatomical sites. The substantial N. gonorrhoeae load at all sample sites suggest that all sites may have transmission potential. However, the oropharyngeal site presents the lowest bacterial load. Men and women have a similar N. gonorrhoeae loads on separate anatomical sites, arguing for similar transmission potential and similar clinical relevance.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.01171-20
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1498353-9
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  • 9
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    Culture-Independent Genotyping Improves Surveillance of Neisseria gonorrhoeae, Especially in Oropharyngeal Samples, the Netherlands, 2017 to 2018
    MDPI AG ; 2022
    In:  Pathogens Vol. 11, No. 11 ( 2022-11-14), p. 1344-
    Details
    In: Pathogens, MDPI AG, Vol. 11, No. 11 ( 2022-11-14), p. 1344-
    Abstract: It is important i to monitor the transmission and antimicrobial resistance of Neisseria gonorrhoeae (NG). Current surveillance relies on culturing, which frequently fails. Previously, a culture-independent genotyping method was developed based on NG multi-antigen sequence typing (NG-MAST). To determine whether crucial sequence types (STs) are missed during culture-dependent surveillance, NG-positive NAAT samples were genotyped, and the results of the culture-positive and culture-negative samples were compared. In total, 196 NG-positive NAAT samples, from January 2017 until August 2018, which were also routinely cultured, were retrospectively included. Genotyping was successful in 152 NAAT samples (77.0%), 33 NAAT samples failed, and 11 NAAT samples showed possible mixed strain infections. Oropharyngeal samples (n = 16) showed the largest increase in typing rate from 6.3% (1/16) success in culture-dependent genotyping to 81.3% (13/16) in culture-independent genotyping. Nine genogroups (n ≥ 5 samples) were found; all included both culture-positive and culture-negative NG. However, culture-independent surveillance revealed 14 additional STs in the culture-negative samples. Overall, culture-dependent surveillance could detect all genogroups, indicating that major trends could be identified with culture-dependent surveillance. However, culture-independent surveillance provides more STs, mixed infections and more oropharyngeal samples, giving a more detailed view and could result in an earlier detection of outbreaks and transmission.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens11111344
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2695572-6
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  • 10
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    Antimicrobial Resistance of Neisseria gonorrhoeae Isolates from High-Risk Men in Johannesburg, South Africa
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 11 ( 2020-10-20)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 11 ( 2020-10-20)
    Abstract: Neisseria gonorrhoeae antimicrobial drug resistance has emerged worldwide; however, the situation in sub-Saharan Africa is not well documented. We investigated the molecular epidemiology and occurrence of antimicrobial resistance in Neisseria gonorrhoeae infections in two core transmission groups of men in Johannesburg, South Africa. We recruited men who have sex with men (MSM) presenting with urethral discharge and men with recurrent episodes of urethral discharge. Molecular testing and culture for N. gonorrhoeae were performed, followed by antimicrobial susceptibility testing. Whole-genome sequencing (WGS) was used to identify resistance-conferring mutations and to determine the genetic relatedness of the isolates. In all, 51 men were recruited; 42 (82%) had N. gonorrhoeae infections. Most gonococcal isolates were resistant to ciprofloxacin (78%) and tetracycline (74%); 33% were penicillin resistant. All gonococcal isolates were susceptible to cephalosporins and spectinomycin. Azithromycin resistance was observed in 4 (15%) isolates (epidemiological cutoff), all with mutations in the mtrR promoter region. Most of the isolates (19/27) harbored the gonococcal genetic island, which is associated with antimicrobial resistance. WGS revealed a diverse epidemic with mostly novel NG-STAR (70%) and NG-MAST (70%) sequence types. Thus, we demonstrate a high prevalence of antimicrobial resistance in Neisseria gonorrhoeae strains obtained from high-risk men in South Africa. The introduction of diagnostics and scale-up of surveillance are warranted to prevent the emergence of multidrug-resistant infections.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00906-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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