Trends in SARS-CoV-2 seroprevalence amongst urban paediatric patients compared with a nationwide cohort in the Netherlands.

Objectives: The extent of SARS-CoV-2 infection amongst children and their role in transmission remains unclear. Therefore, we aimed to estimate the SARS-CoV-2 antibody seroprevalence amongst children who presented to our hospital for non-COVID-19-related morbidity during the first and second epidemic wave in 2020 and compared these to the general Dutch paediatric population. Methods: We collected residual plasma samples from all paediatric patients (1 month-17 years of age) visiting our clinic or emergency room, who had blood drawing for various medical reasons. Samples were analysed for the presence of total antibodies against SARS-CoV-2 by Wantai ELISA. The seroprevalence in two separate periods (July-Sep 2020, and Oct-Dec 2020) was compared to regional and national data (PIENTER-Corona study, September 2020), and associations with co-morbidities were assessed. Results: A total of 209 samples in period 1 and 240 samples in period 2 were collected (median age 7.1 years, IQR 1.5-13.5). SARS-CoV-2 antibodies were detected in 4.1% and 13.8%, respectively (p< 0.001). Seroprevalence was higher compared to national paediatric data, but did not differ with regional estimates. Most children with SARS-CoV-2 antibodies were seen in the outpatient clinic for general paediatric problems with no differences in medical reasons for presentation between the two periods. Conclusions: These data confirm a rapid three-fold increase in SARS-CoV-2 seroprevalence in paediatric patients in the second half of 2020 with a trend towards a higher seroprevalence compared to randomly-selected children in a nationwide study. Underlying morbidity in children might not play an important role in acquiring SARS-CoV-2 infection.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among undocumented migrants and uninsured legal residents in Amsterdam, the Netherlands: a cross-sectional study.

BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased risk of infection. Colonization with MRSA is observed in < 1% of the general Dutch population. Increased risk for MRSA carriage is known to occur in several key groups, one of which is asylum seekers. However, little is known about MRSA carriage among undocumented migrants and uninsured legal residents. This study aimed to determine the prevalence of nasal MRSA carriage among these groups in Amsterdam, the Netherlands. METHODS: In this cross-sectional study, between October 2018 and October 2019, undocumented migrants and uninsured legal residents aged 18 years or older who were able to understand one of the study languages were recruited at an NGO health care facility in Amsterdam, the Netherlands, for general practitioner (GP) consultations. Participants were asked questions on demographics, migration history, antibiotic use and other possible risk factors for MRSA carriage and were screened for nasal MRSA carriage by selective culturing e-swabs. Characteristics of MRSA-negative and MRSA-positive participants were compared using univariable logistic regression analysis with Firth's correction. RESULTS: Of the 3822 eligible patients, 760 were screened for nasal MRSA carriage (19.9%). Of the 760 participants, over half were male (58%; 442/760) and originated mainly from Africa (35%; 267/760), Asia (30%; 229/760) and North or South America (30%; 227/760). In total, 705/760 participants (93%) were undocumented migrants and 55/760 (7%) were uninsured legal residents of Amsterdam. The overall prevalence of nasal MRSA carriage was 2.0% (15/760) (95%CI 1.1 to 3.2%), with no difference between undocumented migrants (14/705) (2.0, 95%CI 1.1 to 3.3%) and uninsured legal residents (1/55) (1.8, 95%CI 0.1 to 9.7%). Genotyping showed no clustering of the 15 isolates. MRSA carriage was not associated with sociodemographic, migration history or other possible risk factors. Nevertheless, this study had limited power to detect significant determinants. Three participants (3/15; 20%) harbored Panton-Valentine leukocidin (PVL)-positive isolates. CONCLUSION: Even though our study population of undocumented migrants and uninsured legal residents had a higher prevalence of nasal MRSA carriage compared to the general Dutch population, the prevalence was relatively low compared to acknowledged other high-risk groups.

Trends in paediatric inpatient antibiotic therapy in a secondary care setting.

There is growing attention for antimicrobial stewardship in paediatrics. Currently, little is known about secondary care antibiotic practice. We analysed trends in time with respect to inpatient antibiotic use in a secondary paediatric care setting. Total inpatient antibiotic consumption per year (2010-2015) and antibiotic prescriptions for urinary tract infection (UTI) and lower respiratory tract infection (LRTI) were analysed. Variables were total, antibiotic-specific, and intravenous days of therapy (DOT/100PD) and for UTI/LRTI treatment type, route and duration. Third-generation cephalosporin use decreased (DOT/100PD 11.6 in 2011 vs. 5.1 in 2015; p < 0.001); intravenous antibiotics were prescribed less often (p = 0.06). These findings were confirmed for the specific diseases: third-generation cephalosporin use decreased for both UTI (93% vs. 45%; p = 0.002) and LRTI (14% vs. 6%; p = 0.18); the duration of intravenous therapy decreased (UTI p = 0.02; LRTI p < 0.001). Median LRTI treatment duration was 9.2 days in 2008 and 6.6 in 2015 (p < 0.001); penicillin prescriptions were more narrow in spectrum (p = 0.02). CONCLUSION: A decrease in third-generation cephalosporin use and intravenous route was identified. LRTI treatment was significantly shorter and more narrow in spectrum. This could be explained by awareness and interventions in the context of antimicrobial stewardship. A decrease in antibiotic use is also feasible and important in non-tertiary paediatric wards. What is Known: • Antimicrobial stewardship programmes are effective in reduction of total and broad-spectrum antibiotic use in tertiary paediatric hospitals • The majority of hospitalised paediatric patients are admitted at general, secondary care wards, often for infectious diseases What is New: • Antimicrobial stewardship interventions in secondary care are also effective in establishing a reduction in broad-spectrum antibiotic use, intravenous route and days on antibiotic therapy.

Undocumented children in the Amsterdam region: an analysis of health, school, and living circumstances.

Undocumented migrants are people who do not have a valid residence permit. There are only estimates about how many undocumented migrants are living in the European Union; the number of children among them is unclear. Studies about undocumented children are scarce and little is known about their living situation and their access to health care. Therefore, we aimed to estimate the number of undocumented children in the population of visitors of our primary care clinic for undocumented patients. Moreover, we explored whether these children's rights with respect to health care, education, and living circumstances were met. All undocumented adult patients visiting the clinic between September 1, 2016 and December 31, 2016 received a questionnaire. In total, 267 undocumented adults responded; 30% of them had children, and 15% had one or more undocumented children living in the Netherlands. Eleven percent of those undocumented children did not attend school, 17% was not vaccinated, 83% did not have a general practitioner, and 30% did not have a permanent place of residence. CONCLUSION: There are probably a considerable number of undocumented children in the Netherlands; our study estimated a percentage of 17% of the undocumented population. Not all their basic human rights are met; more awareness among people involved with child and health policies is needed. What is Known: • There are only estimates of the number of undocumented migrants in the European Union, the number of children among them is not clear. • Studies about undocumented children are scarce and little is known about their living circumstances and access to health care. What is New: • A substantial number of undocumented children do not go to school, are not vaccinated, and do not have a general practitioner. • The hidden group of undocumented children, whose basic human rights are not met, need special attention when they or their caregivers present at a health care facility.

[A child with abdominal pain and fever: consider acute lobar nephritis - diagnostic considerations when the appendix is invisible on ultrasound]. / Kind met buikpijn en koorts: overweeg acute lobaire nefritis.

Acute lobar nephritis (ALN) is a focal interstitial bacterial infection of the renal parenchyma. ALN is described as a midpoint between an acute pyelonephritis and renal abscess. ALN is underdiagnosed in children due to both non-specific symptoms and negative urinalysis/bacteriuria laboratory findings. The gold standard for diagnosis of ALN is CT scanning, however MRI can be considered to avoid radiation exposure. Diagnosing ALN is relevant, because it requires prolonged antibiotic treatment. Insufficient antibiotic treatment could cause renal scarring and subsequent hypertension or renal failure. Outpatient follow-up is indicated to exclude congenital urogenital abnormalities. We describe two paediatric patients with acute abdominal pain and fever who were suspected to have appendicitis (appendix not visualised by ultrasonography), but eventually were diagnosed with ALN and a renal abscess (despite absence of pyuria). These reports serve to highlight the issues around the recognition and diagnosis of ALN in children, and the need for clinicians to be mindful of this condition.

[A teenage girl with non-infectious osteomyelitis]. / Een tiener met een niet-infectieuze osteomyelitis.

BACKGROUND: Osteomyelitis is usually caused by an infection. A non-infectious cause should be considered if antibiotic treatment is insufficiently effective and disease is recurrent, multifocal or migrating. CASE DESCRIPTION: A 14-year-old girl, an active volleyball player, developed episodes of fever and pain in her right lower leg. MRI showed osteomyelitis in her right tibia. She received prolonged intravenous antibiotic treatment. Shortly after recovery, she developed osteomyelitis in her left lower leg. After exclusion of infection and malignancy, we diagnosed chronic recurrent multifocal osteomyelitis (CRMO). The patient was successfully treated with a NSAID and a bisphosphonate. CONCLUSION: CRMO is an auto-inflammatory condition characterised by recurrent, non-infectious, multifocal or migrating osteomyelitis. Patients experience recurrent episodes of bone pain, sometimes accompanied by fever and slightly elevated infection parameters. The disease course usually is self-limiting, without residual damage. Symptomatic treatment with NSAIDs and bisphosphonates often leads to remission.

Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates.

Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments. Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared. Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (p <0.01). None of the isolates were resistant to antibiotics. The isolates were genotypically highly diverse. Multivariate analysis showed that in vitro determined bacterial characteristics could not predict persistence after first P. aeruginosa infection. Preliminary transcriptomic data showed increased expression of some genes related to a metabolic pathway. The early onset of chronic infection was not associated with (in vitro determined) bacterial characteristics only. Although the persistent isolates were more often cytotoxic, for the individual patient it was not possible to predict the risk of persistence based on bacterial characteristics. Unknown factors such as host-pathogen and pathogen-pathogen interactions should be further explored.

Pseudomonas aeruginosa diversity in distinct paediatric patient groups.

Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157 patients (CF first infection (CF-1 group) (29); CF chronic infection (CF-chronic group) (27); urinary tract infection (34); chronic suppurative otitis media (43); and intensive-care hospitalization/immunodeficiency (24)). All 202 phenotypically different isolates were tested for antimicrobial resistance and further typed by pulsed-field gel electrophoresis. Simpson's diversity index was calculated for the five groups. CF-chronic patients carried the highest number of distinct P. aeruginosa phenotypes and genotypes per culture. Isolates from the CF-chronic group were significantly less diverse than those from the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups and among the clonal isolates. In conclusion, isolates of the CF-chronic group were less diverse than those in the other patient groups with P. aeruginosa infection; clonal isolates were not encountered in non-CF patients. Transmission of clonal CF isolates to other patient groups was not observed.

Diagnostic value of serological tests against Pseudomonas aeruginosa in a large cystic fibrosis population.

BACKGROUND: Serological methods to monitor Pseudomonas aeruginosa colonisation in patients with cystic fibrosis (CF) are advocated but the diagnostic value of a commercially available P aeruginosa antibody test to detect early and chronic P aeruginosa colonisation in a non-research setting has not been assessed. METHODS: Colonisation with P aeruginosa was estimated by regular culture of sputum or oropharyngeal swabs during three consecutive years in 220 patients with CF aged 0-65 years. Commercially available ELISA tests with three P aeruginosa antigens (elastase, exotoxin A, alkaline protease) were performed at the end of the study period. In a subgroup of 57 patients (aged 4-14 years) serological tests were performed annually. RESULTS: Using culture as the reference standard, the ELISA tests using the advised cut off values had a sensitivity of 79% and a specificity of 89% for chronic colonisation. Receiver-operator characteristic curves were created to optimise cut off values. Applying these new cut off values resulted in a sensitivity of 96% and a specificity of 79%. All three individual serological tests discriminated well between the absence and presence of chronic P aeruginosa colonisation. The sensitivity of the individual antibody test was 87% for elastase, 79% for exotoxin A, and 76% for alkaline protease. First colonisation was preceded by positive serological results in only five of 13 patients (38%). CONCLUSION: In patients with CF, serological tests using specific antigens are sensitive for diagnosing chronic P aeruginosa colonisation. However, the failure of serological tests to detect early colonisation in young patients emphasises the need for continued reliance on cultures.

Detection of Pseudomonas aeruginosa in patients with cystic fibrosis.

Chronic pulmonary colonisation with Pseudomonas aeruginosa (PA) in patients with CF is associated with a high morbidity and mortality. Adequate treatment of first acquisition of PA might prevent or postpone chronic colonisation. Early detection of PA is therefore of major importance. Currently, cultures of oropharynx or sputum are most commonly practised. However, oropharyngeal culture has limitations both in the positive and negative predictive value for the presence of PA in the lower respiratory tract. Induction of sputum has little benefit in detection of PA. Serology might have additional value in early detection, when bacterial density is too low to be detected by culture. Molecular techniques are not yet widespread used for detection of PA, but have in general a high sensitivity. In this review, we describe the value of different diagnostic techniques for detecting PA.