Effect of lockdowns on the epidemiology of pediatric respiratory disease-A retrospective analysis of the 2021 summer epidemic.

BACKGROUND: The imposition of lockdowns during the severe acute respiratory syndrome coronavirus-2 pandemic led to a significant decrease in pediatric care utilization in 2020. After restrictions were loosened, a surge in pediatric respiratory disease was observed in pediatric wards. The aim of this study was to quantify the effect of the lockdown(s) on the incidence of pediatric respiratory disease. METHODS: For this multicenter retrospective study, emergency department (ED) visit and admission data between January 2017 and September 2021 was collected from eight general hospitals in the Netherlands. Clinical diagnoses were extracted and categorized in groups ("communicable infectious disease," "all respiratory infections," "upper respiratory tract infection," "lower respiratory tract infection," and "asthma/preschool wheezing"). The incidence of admissions and ED visits during 2020 and 2021 was compared to the incidence in 2017-2019. RESULTS: Successive lockdowns resulted in a maximum decrease of 61% and 57% in ED visits and admissions, respectively. After loosening restrictions during the summer of 2021, a 48% overall increase in ED visits and 31% overall increase in admission numbers was observed in July compared to the average July in 2017-2019. This was explained by a 381% increase in ED visits and a 528% increase in ward admissions due to overall respiratory infections, mainly due to lower respiratory tract infections. CONCLUSIONS: Successive lockdowns in the spring and winter of 2020 and 2021 led to a decreased incidence of communicable infections, especially respiratory tract infections. The resulting lack of pediatric immunity resulted in an off-season surge in care utilization at an unexpected moment.

Livestock-associated methicillin-resistant Staphylococcus aureus epidemiology, genetic diversity, and clinical characteristics in an urban region.

Objectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population. Methods: In this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes. Results: LA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates). Conclusion: LA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures.

A Clinical Prediction Model for Surgical Site Infections in Dermatological Surgery.

To adequately identify patients at risk for surgical site infection in dermatological surgery and effectively prescribe antibiotic prophylaxis, a prediction model may be helpful. Such a model was developed using data from 1,407 patients who underwent dermatological surgery without antibiotic prophylaxis. The multivariable logistic regression model included type of closure, tumour location and defect size as risk factors. Bootstrapping was used for internal validation. The overall performance of the model was good, with an area under the curve of 84.1%. The decision curve analysis showed that the model is potentially useful if one is willing to treat more than 8 patients with antibiotic prophylaxis to avoid one infection. For those who prefer more restrictive use of antibiotic prophylaxis, a default strategy of treating no patients at all with prophylaxis would be the best choice. External validation of the model is required before it can be widely applied.

First human case of tick-borne encephalitis virus infection acquired in the Netherlands, July 2016.

In July 2016, the first autochthonous case of tick-borne encephalitis was diagnosed in the Netherlands, five days after a report that tick-borne encephalitis virus (TBEV) had been found in Dutch ticks. A person in their 60s without recent travel history suffered from neurological symptoms after a tick bite. TBEV serology was positive and the tick was positive in TBEV qRT-PCR. TBEV infection should be considered in patients with compatible symptoms in the Netherlands.

Colonization dynamics of antibiotic-resistant coagulase-negative Staphylococci in neonates.

Coagulase-negative staphylococci (CoNS) isolated in neonatal late-onset sepsis are often antibiotic resistant. We analyzed CoNS from skin and feces of neonates during hospitalization. Antibiotic resistance of skin isolates increased during hospitalization, especially in Staphylococcus haemolyticus. Staphylococcus warneri showed low antibiotic resistance. Our data suggest that different CoNS species may play distinct roles in colonization.

Vaccination with SesC decreases Staphylococcus epidermidis biofilm formation.

The increased use of medical implants has resulted in a concomitant rise in device-related infections. The majority of these infections are caused by Staphylococcus epidermidis biofilms. Immunoprophylaxis and immunotherapy targeting in vivo-expressed, biofilm-associated, bacterial cell surface-exposed proteins are promising new approaches to prevent and treat biofilm-related infections, respectively. Using an in silico procedure, we identified 64 proteins that are predicted to be S. epidermidis surface exposed (Ses), of which 36 were annotated as (conserved) hypothetical. Of these 36 proteins, 5 proteins-3 LPXTG motif-containing proteins (SesL, SesB, and SesC) and 2 of the largest ABC transporters (SesK and SesM)-were selected for evaluation as vaccine candidates. This choice was based on protein size, number of antigenic determinants, or the established role in S. epidermidis biofilm formation of the protein family to which the candidate protein belongs. Anti-SesC antibodies exhibited the greatest inhibitory effect on S. epidermidis biofilm formation in vitro and on colonization and infection in a mouse jugular vein catheter infection model that includes biofilms and organ infections. Active vaccination with a recombinant truncated SesC inhibited S. epidermidis biofilm formation in a rat model of subcutaneous foreign body infection. Antibodies to SesC were shown to be opsonic by an in vitro opsonophagocytosis assay. We conclude that SesC is a promising target for antibody mediated strategies against S. epidermidis biofilm formation.

Coagulase-negative staphylococcal skin carriage among neonatal intensive care unit personnel: from population to infection.

Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in neonatal intensive care units (NICU) worldwide. Infecting strains of these commensal bacteria may originate from NICU personnel. Therefore, we studied the characteristics of CoNS isolates from NICU personnel and compared them to those of isolates from the general population and from sepsis patients. Furthermore, we studied the epidemiological effect on CoNS carriage of NICU personnel after a period of absence. In our study, we isolated CoNS from the thumbs of NICU personnel every 2 weeks during the summer of 2005 and sampled personnel returning from vacation and a control group from the general population. Furthermore, we collected sepsis isolates from this period. Isolates were tested for antibiotic resistance, mecA and icaA carriage, biofilm production, and genetic relatedness. We found that mecA and icaA carriage as well as penicillin, oxacillin, and gentamicin resistance were significantly more prevalent in CoNS strains from NICU personnel than in community isolates. Similar trends were observed when postvacation strains were compared to prevacation strains. Furthermore, genetic analysis showed that 90% of the blood isolates were closely related to strains found on the hands of NICU personnel. Our findings revealed that CoNS carried by NICU personnel differ from those in the general population. Hospital strains are replaced by community CoNS after a period of absence. NICU personnel are a likely cause for the cross-contamination of virulent CoNS that originate from the NICU to patients.

Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein.

Several well-studied proteins with defined roles in Staphylococcus epidermidis biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (S. epidermidis surface protein C; accession no. NP_765787) as a target for antibodies to prevent biofilm formation. In vitro and in a in vivo rat model of catheter infection, gene and protein expression analysis showed that SesC is expressed more strongly in biofilm-associated cells than in planktonic cells and is expressed particularly during the late phase of in vivo biofilm formation. Polyclonal rabbit antibodies raised against SesC reduced the fibrinogen-binding ability of S. epidermidis RP62A and Staphylococcus aureus RN4220 transformants expressing SesC, inhibited in vitro biofilm formation by S. epidermidis strains 10b and 1457, and significantly reduced the numbers of bacteria in a 1-day-old in vivo biofilm (P < 0.001, one-way analysis of variance). Our findings revealed that SesC is a promising target for prevention and treatment of S. epidermidis biofilms because it affects both the primary attachment and biofilm accumulation phases. The precise role of SesC in biofilm formation remains to be identified.

Clinical and molecular epidemiologic characteristics of coagulase-negative staphylococcal bloodstream infections in intensive care neonates.

OBJECTIVES: This study aimed to determine clinical characteristics of coagulase-negative staphylococcal (CoNS) sepsis in neonates, to assess the molecular epidemiology and biofilm forming properties of isolated strains, and to assess antibiotic susceptibility of clonal compared with incidentally occurring strains. METHODS: We performed a retrospective study on late-onset CoNS sepsis in infants in the neonatal intensive care unit of a Dutch university hospital in 2003. CoNS isolates were genotyped by restriction fragment end labeling and pulsed-field gel electrophoresis. Resistance profiles, biofilm production, and the presence of mecA and icaA were determined. RESULTS: Twenty-six percent of all 339 infants developed late-onset sepsis, 66% of these with CoNS sepsis. Eighty-six percent of all CoNS sepsis occurred in very low birth weight infants. Sixty-six CoNS strains were isolated. In multivariate analysis, small for gestational age and prolonged hospitalization were associated with CoNS sepsis. Among 3 restriction fragment end labeling clusters, we found 1 large cluster comprising 32% of the isolates. Biofilm producing Staphylococcus epidermidis were more frequently icaA positive than nonbiofilm formers (74% vs. 12%; P < 0.001). In other species, this association was not found. Nearly all isolates were resistant to antibiotics. MecA was present in 87% of the isolates. Multiresistance occurred in 77% of all strains and in 73% of clustered strains. There was significantly less multiresistance among the largest cluster. CONCLUSIONS: Small for gestational age and prolonged hospitalization were associated with CoNS sepsis. The icaA gene is a predictor for biofilm formation in S. epidermidis, but not in other species. Multiresistance is not associated with clonality.

Translationally controlled tumor protein from Madurella mycetomatis, a marker for tumorous mycetoma progression.

About 40 years ago Abs against the fungus Madurella mycetomatis were first demonstrated to be present in eumycetoma patients, a disease characterized by tumorous swellings. To date nothing is known about the individual immunoreactive Ags present in this fungus. In the present study, we identify its first immunogenic Ag, a protein homologous to the translationally controlled tumor protein (TCTP), a well-conserved histamine release factor in a range of eukaryotes. The gene for this Ag was demonstrated to be present in two variants in M. mycetomatis, with 13% aa difference between the two proteins encoded. In vitro, TCTP was secreted into the culture medium. In vivo, it was found to be expressed on hyphae present in developing stages of the eumycetoma-characteristic black grain. Significant IgG and IgM immune responses, against the whole protein and selected M. mycetomatis-specific peptides, were determined. The Ab levels correlated with lesion size and disease duration. Overall, the patients with the largest lesions had the highest Ab level, which lowered with decreasing size of the lesion. After 6-15 years of disease duration the Ab levels were the highest. TCTP is the first well-characterized immunogenic Ag, simultaneously the first monomolecular vaccine candidate, identified for the fungus M. mycetomatis.

A new method for analysis of AZT-triphosphate and nucleotide-triphosphates.

We have developed a new method based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) for analysis of zidovudine-triphosphate and (deoxy)nucleotide-triphosphates, which ultimately can be used for nucleoside reverse transcriptase inhibitor (NRTI) treatment monitoring in HIV-1 infected children and adults. Four different matrices were compared for sensitivity and reproducibility of zidovudine-triphosphate detection and anthranilic acid mixed with nicotinic acid (AA/NA) was selected as most suitable matrix. Solutions of zidovudine-triphosphate, ATP, and dGTP were detected up to 0.5fmol per sample. Furthermore, intracellular zidovudine-triphosphate, ATP, and dGTP were detected in peripheral blood mononuclear cells (PBMCs). Zidovudine-triphosphate, ATP, and dGTP yield identical mass spectra, however MALDI-TOF post-source decay analysis can be used for discrimination between these compounds. We conclude that this method based on MALDI-TOF MS can be used for analysis of intracellular zidovudine-triphosphate and (deoxy)nucleotide-triphosphates in PBMCs.