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Showing papers by "Paul H. M. Savelkoul published in 2022"


Journal ArticleDOI
TL;DR: In this paper , the authors compared the viral load in 16,185 samples that were obtained in periods during which non-VOC, the Alpha (B.1.7) or Delta variant were dominant as evidenced by genomic surveillance, and found that the Delta variant contained about fourfold higher viral loads across all age groups compared to the non VOC or Alpha variants.
Abstract: 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.

16 citations


Journal ArticleDOI
TL;DR: In this paper , the authors assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age.
Abstract: Immunoglobulin A (IgA) plays an important role in maintaining a healthy intestinal microbiome, but little is known about the interaction between local immunoglobulins and the vaginal microbiome. We assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age.In both Lactobacillus crispatus-dominated and non-L. crispatus-dominated microbiota, IgA and IgG (unbound and bound to bacteria) were higher during menses (T = 1) compared to day 7‑11 (T = 2) and day 17‑25 (T = 3) after menses onset. The majority of vaginal bacteria are coated with IgA and/or IgG. Women with L. crispatus-dominated microbiota have increased IgA coating of vaginal bacteria compared to women with other microbiota compositions, but contained less IgA per bacterium. Presence of a dominantly IgA-coated population at T = 2 and/or T = 3 was also strongly associated with L. crispatus-dominated microbiota. In women with non-L. crispatus-dominated microbiota, more bacteria were uncoated. Unbound IgA, unbound IgG, and bound IgG levels were not associated with microbiota composition.In conclusion, L. crispatus-dominated vaginal microbiota have higher levels of bacterial IgA coating compared to non-L. crispatus-dominated vaginal microbiota. Similar to its regulating function in the intestinal tract, we hypothesize that IgA is involved in maintaining L. crispatus-dominated microbiota in the female genital tract. This may play a role in L. crispatus-associated health benefits. Video abstract.

6 citations


Journal ArticleDOI
TL;DR: In this article , the authors assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age.
Abstract: Immunoglobulin A (IgA) plays an important role in maintaining a healthy intestinal microbiome, but little is known about the interaction between local immunoglobulins and the vaginal microbiome. We assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age.In both Lactobacillus crispatus-dominated and non-L. crispatus-dominated microbiota, IgA and IgG (unbound and bound to bacteria) were higher during menses (T = 1) compared to day 7‑11 (T = 2) and day 17‑25 (T = 3) after menses onset. The majority of vaginal bacteria are coated with IgA and/or IgG. Women with L. crispatus-dominated microbiota have increased IgA coating of vaginal bacteria compared to women with other microbiota compositions, but contained less IgA per bacterium. Presence of a dominantly IgA-coated population at T = 2 and/or T = 3 was also strongly associated with L. crispatus-dominated microbiota. In women with non-L. crispatus-dominated microbiota, more bacteria were uncoated. Unbound IgA, unbound IgG, and bound IgG levels were not associated with microbiota composition.In conclusion, L. crispatus-dominated vaginal microbiota have higher levels of bacterial IgA coating compared to non-L. crispatus-dominated vaginal microbiota. Similar to its regulating function in the intestinal tract, we hypothesize that IgA is involved in maintaining L. crispatus-dominated microbiota in the female genital tract. This may play a role in L. crispatus-associated health benefits. Video abstract.

6 citations


Journal ArticleDOI
TL;DR: In this article , the authors performed a systematic review, including cluster randomized clinical trials investigating the effect of interventions targeted at GPs to improve antibiotic prescriptions for UTI, finding that most studies employed multifaceted interventions, most frequently including audit & feedback and/or educational meetings.
Abstract: Urinary tract infections (UTIs) are the most common reason for women to consult a general practitioner (GP). While UTIs are self-limiting in half of cases, most women are prescribed antibiotics, often in discordance with established guidelines. Researchers have employed different interventions to improve GPs’ prescribing behavior, especially for respiratory infections, but it is uncertain whether these are effective for UTI care. Therefore, we performed a systematic review, including (cluster) randomized clinical trials investigating the effect of interventions targeted at GPs to improve antibiotic prescriptions for UTI. From September to December 2021 we searched the Medline, Web of Science, and CENTRAL databases, ultimately including ten studies describing eleven trials. We determined the effect of the interventions on the decision to prescribe and on the choice of antibiotic. Results showed that most studies employed multifaceted interventions, most frequently including audit & feedback and/or educational meetings. Seven out of nine trials that recorded first-choice prescriptions saw an increased proportion of first-choice antibiotics in the intervention groups compared to control groups. The employed interventions also caused a decreased proportion of at least one broad-spectrum antibiotic in five out of six studies that measured broad-spectrum antibiotic prescriptions. However, the total number of antibiotic prescriptions for UTIs increased in four out of eight studies. Therefore, while effective at influencing GPs’ prescribing behavior, future interventions should also focus on improving the decision to prescribe at all.

3 citations


Journal ArticleDOI
01 May 2022-BMJ Open
TL;DR: Women are quite receptive to delayed antibiotics as an alternative to immediate antibiotics for UTIs or urinary symptoms, and GPs should consider discussing delayed antibiotic treatment more often with women presenting with urinary symptoms.
Abstract: Objectives Urinary tract infections (UTIs) are the most prevalent cause for women to consult a general practitioner (GP) and are commonly treated with (broad-spectrum) empirical antibiotics, even though 50% of UTIs are self-limiting. In this study, we aim to explore women’s attitudes and experiences regarding UTIs, in order to determine patients’ willingness to accept delayed antibiotic prescriptions. Design An internet-based cross-sectional survey Setting We recruited participants during 2 weeks of March and April in 2020 through several social media platforms. Participants We obtained 1476 responses, of which 975 were eligible for analysis. Results We asked women about their knowledge, attitudes and practice regarding UTI-related symptoms. Participants ranked ‘confirmation of diagnosis’ (43.8%) as the most important reason to consult a GP with urinary symptoms, followed by ‘pain relief’ (32%), and ‘antibiotic prescription’ (14.3%). For treatment, 71% of participants reported that their GP prescribed immediate antibiotics, while only 3% received a delayed antibiotic prescription and 1% was advised pain medication. Furthermore, 50% of respondents were aware of the possible self-limiting course of UTIs and 70% would be willing to accept delayed antibiotic treatment, even if a certain diagnosis of UTI was established. Willingness to delay was lower in experienced patients compared to inexperienced patients. Conclusions Women are quite receptive to delayed antibiotics as an alternative to immediate antibiotics for UTIs or urinary symptoms. GPs should consider discussing delayed antibiotic treatment more often with women presenting with urinary symptoms.

2 citations


Journal ArticleDOI
TL;DR: In this article , a tool called the Infection Risk Scan (IRIS) was developed to measure the quality of infection control and antimicrobial use in nine hospitals in the Dutch/Belgian border area and obtained results.
Abstract: A tool, the Infection Risk Scan has been developed to measure the quality of infection control and antimicrobial use. This tool measures various patient-, ward- and care-related variables in a standardized way. We describe the implementation of this tool in nine hospitals in the Dutch/Belgian border area and the obtained results.The IRIS consists of a set of objective and reproducible measurements: patient comorbidities, (appropriate) use of indwelling medical devices, (appropriate) use of antimicrobial therapy, rectal carriage of Extended-spectrum beta-lactamase producing Enterobacterales and their clonal relatedness, environmental contamination, hand hygiene performance, personal hygiene of health care workers and presence of infection prevention preconditions. The Infection Risk Scan was implemented by an expert team. In each setting, local infection control practitioners were trained to achieve a standardized implementation of the tool and an unambiguous assessment of data.The IRIS was implemented in 34 wards in six Dutch and three Belgian hospitals. The tool provided ward specific results and revealed differences between wards and countries. There were significant differences in the prevalence of ESBL-E carriage between countries (Belgium: 15% versus The Netherlands: 9.6%), environmental contamination (median adenosine triphosphate (ATP) level Belgium: 431 versus median ATP level The Netherlands: 793) and calculated hand hygiene actions based on alcohol based handrub consumption (Belgium: 12.5/day versus The Netherlands: 6.3/day) were found.The Infection risk Scan was successfully implemented in multiple hospitals in a large cross-border project and provided data that made the quality of infection control and antimicrobial use more transparent. The observed differences provide potential targets for improvement of the quality of care.

1 citations


Journal ArticleDOI
TL;DR: In this paper , a tool called the Infection Risk Scan (IRIS) was developed to measure the quality of infection control and antimicrobial use in nine hospitals in the Dutch/Belgian border area and obtained results.
Abstract: A tool, the Infection Risk Scan has been developed to measure the quality of infection control and antimicrobial use. This tool measures various patient-, ward- and care-related variables in a standardized way. We describe the implementation of this tool in nine hospitals in the Dutch/Belgian border area and the obtained results.The IRIS consists of a set of objective and reproducible measurements: patient comorbidities, (appropriate) use of indwelling medical devices, (appropriate) use of antimicrobial therapy, rectal carriage of Extended-spectrum beta-lactamase producing Enterobacterales and their clonal relatedness, environmental contamination, hand hygiene performance, personal hygiene of health care workers and presence of infection prevention preconditions. The Infection Risk Scan was implemented by an expert team. In each setting, local infection control practitioners were trained to achieve a standardized implementation of the tool and an unambiguous assessment of data.The IRIS was implemented in 34 wards in six Dutch and three Belgian hospitals. The tool provided ward specific results and revealed differences between wards and countries. There were significant differences in the prevalence of ESBL-E carriage between countries (Belgium: 15% versus The Netherlands: 9.6%), environmental contamination (median adenosine triphosphate (ATP) level Belgium: 431 versus median ATP level The Netherlands: 793) and calculated hand hygiene actions based on alcohol based handrub consumption (Belgium: 12.5/day versus The Netherlands: 6.3/day) were found.The Infection risk Scan was successfully implemented in multiple hospitals in a large cross-border project and provided data that made the quality of infection control and antimicrobial use more transparent. The observed differences provide potential targets for improvement of the quality of care.

1 citations


Journal ArticleDOI
TL;DR: In this article , the effect of selective decontamination of the digestive tract (SDD) is evaluated in a large homogenous group of elective colorectal cancer surgery patients.
Abstract: Selective decontamination of the digestive tract (SDD) is aimed at elimination of potential pathogenic microorganisms. In this study, the effect of SDD on gut microbiota was evaluated in a large homogenous group of elective colorectal cancer surgery patients. Rectal swabs were taken from 118 patients undergoing colorectal surgery. These patients were randomly assigned to receive perioperative SDD or to the control group (no SDD). Rectal swabs were taken prior to surgery, 3 days after commencing administration of SDD. Gut microbial profiles were obtained with the IS-pro technique, a standardized microbiota profiling assay applicable in clinical routine. Differences in abundance for different taxonomical groups and diversity between the groups were assessed. Unsupervised and supervised classification techniques were used to assess microbial signatures, differentiating between the SDD group and the control group. Patients in the SDD group had different gut microbial signatures than in the control group, also in phyla that are not a target for SDD. Escherichia coli, Sutterella spp., Faecalibacterium prausnitzii, and Streptococcus spp. were the species that differed the most between the two groups. The SDD group showed clustering into two subgroups. In one subgroup, a decrease in Proteobacteria was observed, whereas the other subgroup showed a shift in Proteobacteria species. This study shows that SDD not only decreases colonization of the gastrointestinal tract with potential pathogenic Gram-negative microorganisms, but also reduces the abundance of normal colonizers of our gastrointestinal system and leads to a shift in total microbiota composition.

Journal ArticleDOI
TL;DR: It is shown that sex and age differences in the proportion experienced symptoms by serostatus in a large cohort of both unaware (untested) seropositive compared with seronegative reference participants can contribute to timely identification of infection, gaining importance once governments currently move away from mass testing again.
Abstract: Abstract We examined the possible sex and age differences in the proportion of experienced Coronavirus Disease 2019 (COVID-19) symptoms in unaware (previously) infected adults, and their uninfected counterparts, estimated by serostatus prior to vaccination, at the end of 2020 (Wuhan strain). A cross-sectional community-based study using a convenience sample of 10 001 adult inhabitants of a southern Dutch province, heavily affected by COVID-19, was conducted. Participants donated a blood sample to indicate past infection by serostatus (positive/negative). Experienced symptoms were assessed by questionnaire, before the availability of the serological test result. Only participants without confirmed SARS-CoV-2 infection were included (n = 9715, age range 18–90 years). The seroprevalence was comparable between men (17.3%) and women (18.0%), and participants aged 18–60 years (17.3%) and aged 60 years and older (18.6%). We showed sex and age differences in the proportion experienced symptoms by serostatus in a large cohort of both unaware (untested) seropositive compared with seronegative reference participants. Irritability only differed by serostatus in men (independent of age), while stomach ache, nausea and dizziness only differed by serostatus in women aged 60 years and older. Besides, the proportion of experiencing pain when breathing and headache differed by serostatus in men aged 18–60 years only. Our study highlights the importance of taking possible sex and age differences into account with respect to acute and long-term COVID-19 outcomes. Identifying symptom profiles for sex and age subgroups can contribute to timely identification of infection, gaining importance once governments currently move away from mass testing again.

Journal ArticleDOI
20 Apr 2022-PLOS ONE
TL;DR: In Staphylococcus aureus bacteremia pathogen-specific BDL is distinctly higher in patients with intravascular infections compared to extravascular origins, and can improve the diagnostic work-up of SAB by rapidly identifying the subset of patients who need higher dosages of antibiotics and additional measures to improve outcome.
Abstract: Objectives Determination of pathogen-specific bacterial DNA load (BDL) in blood has been shown to be directly correlated with severity of infection in patients with bacteremia. In the diagnostic work-up of patients with Staphylococcus aureus bacteremia (SAB), determination of the primary focus is imperative, because of implications for treatment duration, and ultimately prognosis. Here we investigate whether measurement of BDL in patients with SAB can distinguish between intravascular and extravascular foci of infection. Methods In a consecutive cohort of 43 patients with positive blood cultures with Staphylococcus aureus, we performed a quantitative PCR on whole blood to detect the bacterial DNA load. Infections were classified into 3 categories: i) soft tissue infections and phlebitis, ii) deep-seated infections and iii) endocarditis and other intravascular infections. Bacterial DNA loads and inflammatory parameters in the three categories were analyzed and compared. Results Median BDL in patients with endocarditis and other intravascular infections was 1015 cfu/ml, significantly higher than BDL in the other two categories (28 and 31 cfu/ml respectively). In contrast, CRP and leukocytes were not significantly different between the three patient categories. BDL could be detected in all patients with intravascular causes and levels were generally 10–30 times higher than in the other infection categories. Median BDL in non-survivors was 85 cfu/ml, which was higher than in survivors with a median BDL of 29 cfu/ml, although not significant. Conclusions In Staphylococcus aureus bacteremia pathogen-specific BDL is distinctly higher in patients with intravascular infections compared to extravascular origins. As measurement of BDL by PCR can easily be implemented in routine diagnostics, it can improve the diagnostic work-up of SAB by rapidly identifying the subset of patients who need higher dosages of antibiotics and additional measures to improve outcome.

Journal ArticleDOI
15 Aug 2022
TL;DR: Assessment of commonly used contact lens disinfectants against severe acute respiratory syndrome corona virus 2 found that disinfectant solutions effectively disinfect CLs from SARS-CoV-2 if manufacturer's instructions are followed.
Abstract: Objective: To assess the effect of commonly used contact lens disinfectants against severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Methods: The efficacy of five disinfectant solutions against SARS-CoV-2 was tested in the presence and absence of contact lenses (CLs). Three types of unused CLs (hard gas permeable, soft hydrogel, and soft silicone hydrogel) and worn silicone hydrogel CLs were tested. Contact lenses were infected with SARS-CoV-2 and disinfected at various times, with and without rubbing and rinsing, as per manufacturer's instructions. Reverse-transcriptase polymerase chain reaction (RT-PCR) and viability polymerase chain reaction (PCR) were applied to detect SARS-CoV-2 RNA and viral infectivity of SARS-CoV-2, respectively. Results: In the presence of SARS-CoV-2–infected CLs, no SARS-CoV-2 RNA could be detected when disinfectant solutions were used according to the manufacturer's instructions. When SARS-Co-V2–infected CLs were disinfected without the rub-and-rinse step, SARS-CoV-2 RNA was detected at almost each time interval with each disinfecting solution tested for both new and worn CLs. In the absence of CLs, viable SARS-CoV-2 was detected with all disinfectant solutions except Menicon Progent at all time points. Conclusions: Disinfectant solutions effectively disinfect CLs from SARS-CoV-2 if manufacturer's instructions are followed. The rub-and-rinse regimen is mainly responsible for disinfection. The viability PCR may be useful to indicate potential infectiousness.