Annemarie M van Rossum

Erasmus MC University Medical Center Rotterdam · Dept of Pediatrics/Infectious Diseases and Immunology and Dept of Medical Microbiology and Infectious Diseases

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of cu...

Objectives We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding. Methods This is a case report from a Dutch academic hospit...

Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on...

Mycoplasma pneumoniae is an important cause of pneumonia and extra-pulmonary manifestations. We observed a rise in admissions due to M. pneumoniae infections starting October 2023 in a regional hospital in the Netherlands and an increased incidence in national surveillance data. The incidence in the Netherlands has not been that high since 2011. Th...

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet’s- and inflammatory bowel disease (IBD)-like disorder termed “deficiency in ELF4, X-linked” (DEX) affec...

Background Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associate...

Objectives To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children’s adoption status. Design A prospective population-based open cohort including children with PHI...

The worldwide increase in the incidence of antibiotic resistance of the atypical bacterium Mycoplasma pneumoniae (MP) challenges the treatment of MP infections, especially in children. Therefore, alternative strategies for the treatment of MP infections are warranted. Galacto- and fructo-oligosaccharides (GOS and FOS) are a specific group of comple...

Dolutegravir 50 mg is registered for use in children weighing 20-40 kg. This approval is based on data from an African paediatric cohort, and no pharmacokinetic data was available from children outside of Africa. This study provides further evidence of the effective use of dolutegravir 50 mg in children weighing 20-40 kg by showing adequate doluteg...

Background: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries inclu...

Mycoplasma pneumoniae and Streptococcus pneumoniae are the most common bacterial causes of pneumonia in children. The clinical characteristics of pneumonia differ significantly between the two bacteria. We aimed to elucidate the differences in pathogenesis between M. pneumoniae and S. pneumoniae by characterizing the respiratory epithelial cell imm...

Objectives . SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity compared to earlier variants. Therefore, we aimed to assess and classify the cause of hospitalization for COVID-19 patients identified with these Omicron variants within our hospital. Methods . A retrospective analysis was performed on all patients identi...

Although fatigue is a common symptom in adult patients with primary immunodeficiencies (PID), data in pediatric patients are limited. The goal of this study is to estimate the prevalence and impact of fatigue in children with PID as reported by patients, parents, and health-care providers. A retrospective single-center observational study was perfo...

SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity. We classified 172 COVID-19 Omicron patient admissions. 66.2% of patients were admitted with primary or admission-contributing COVID-19. We therefore must be careful to base healthcare and public health decisions on the total number of hospitalized COVID-19 patients al...

Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and...

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advan...

Early-life viral infection can have profound effects on the developing lung and immune systems, both important in asthma development. For decades, research has aimed to establish whether there is a causal link between these viral infections as an exposure and asthma later in childhood. Establishing causality will remain important, but new insights...

Background: Defects in IFN–gamma receptor (IFN-γR) signaling via STAT1 leads to susceptibility to infection by otherwise weak pathogenic mycobacteria, resulting in mendelian susceptibility to mycobacterial disease. We identified three patients presented with disseminated mycobacterial infections caused by M. avium, M. persicum or M. bovis BCG respe...

Backgrounds The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-mini...

Objectives To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. Methods Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered:...

Advances in antiretroviral treatment improved the life expectancy of perinatally HIV-infected children. However, growing up with HIV provides challenges in daily functioning. This cross-sectional cohort study investigated the neuropsychological and psychosocial functioning of a group of perinatally HIV-infected children in the Netherlands and compa...

Mycoplasma pneumoniae is the most common bacterial cause of pneumonia in children hospitalised for community-acquired pneumonia. Prevention of infection by vaccines may be an important strategy in the presence of emerging macrolide resistant M. pneumoniae. However, knowledge of immune responses to M. pneumoniae is limited, complicating vaccine desi...

Background: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EO...

Transcription factors specialized to limit the destructive potential of inflammatory immune cells remain ill-defined. We discovered loss-of-function variants in the X-linked ETS transcription factor gene ELF4 in multiple unrelated male patients with early onset mucosal autoinflammation and inflammatory bowel disease (IBD) characteristics, including...

Introduction: Respiratory tract infections (RTIs) affect children all over the world and are associated with significant morbidity and mortality. In particular, recurrent RTIs cause a high burden of disease and lead to frequent doctor visits. Children with recurrent RTIs generally have no significant alterations or deficits in systemic immunity. I...

Bacterial respiratory tract infections (RTIs) are a major global health burden, and the role of antigen-presenting cells (APCs) in mounting an immune response to contain and clear invading pathogens is well-described. However, most encounters between a host and a bacterial pathogen do not result in symptomatic infection, but in asymptomatic carriag...

Lower respiratory tract infections (LRTIs) in children are common and, although often mild, a major cause of mortality and hospitalization. Recently, the respiratory microbiome has been associated with both susceptibility and severity of LRTI. In this current study, we combined respiratory microbiome, viral, and clinical data to find associations w...

IFN–gamma receptor (IFNGR) signaling via STAT1 is crucial in the defense against intracellular pathogens. Defects in this pathway enhance the susceptibility to infection by otherwise weak pathogenic mycobacteria, resulting in a primary immunodeficiency called mendelian susceptibility to mycobacterial disease (MSMD). Here we describe three patients...

Introduction Since the introduction of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection is a manageable chronic disease. However, school-age children (4–18 years) living with HIV could still experience problems with functioning at school, due to the impact of the virus itself, medication, comorbidities and social sti...

Ureaplasma species are increasingly recognized as relevant pathogens in prenatal, perinatal and postnatal morbidity. They are commonly found as commensals on the mucous membranes of the lower urogenital tract of pregnant women, but when ascending, they can cause bacterial vaginosis, chorioamnionitis, premature birth and postnatal morbidities such a...

The Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) pandemic impacted the organization of paediatric hospitals. This study aimed to evaluate the preparedness for the pandemic among a European network of children's hospitals and to explore the strategies to restart health care services. A cross-sectional, web-based survey was distr...

Although fatigue is a common symptom in adult patients with Primary Immunodeficiencies (PID), data in pediatric patients are limited. The goal of this study is to estimate the prevalence and impact of fatigue in children with PID as reported by patients, parents and health-care providers. A retrospective single center observational study was perfor...

Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influ...

Objectives To provide a comprehensive assessment of case stratification by the Neonatal Early-Onset Sepsis (EOS) Calculator, a novel tool for reducing unnecessary antibiotic treatment. Study design A systematic review with individual patient data meta-analysis was conducted, extending PROSPERO record CRD42018116188. Cochrane, PubMed/MEDLINE, EMBAS...

Background: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. Methods: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomize...

Background: The early onset sepsis (EOS) calculator was developed and validated in a setting with routine-based Group B Streptococcus (GBS) screening. Purpose: The aim was to evaluate to what extent a risk-based GBS screening influences management recommendations by the EOS calculator. Methods: All newborns with a gestational age of more than...

Background: We recently demonstrated that the measurement of Mycoplasma pneumoniae (Mp)-specific IgM antibody-secreting cells (ASCs) improved diagnosis of Mp infection. Here, we aimed to describe Mp ASC kinetics and duration in comparison to conventional measures such as pharyngeal Mp DNA and serum antibodies. Methods: Prospective longitudinal s...

Background: There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific IgM antibody-secr...

Importance The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation. Objective To assess the association between managem...

Biomedical scientists aim to contribute to further understanding of disease pathogenesis and to develop new diagnostic and therapeutic tools that relieve disease burden. Yet the majority of biomedical scientists do not develop their academic career or professional identity as “translational scientists,” and are not actively involved in the continuu...

Mycoplasma pneumoniae (Mp) is reported to be the most common bacterial cause of community-acquired pneumonia (CAP) in hospitalized U.S. children (1). However, current diagnostic tests, including PCR of upper respiratory tract (URT) specimens and serology, do not differentiate between Mp infection and carriage (2). Mp carriage in the URT is found in...

Biomarkers have become an integral part of the clinical decision-making process of clinicians dealing with febrile children. C-reactive protein, procalcitonin and white blood cell count are probably the most studied ones. Crucial to using biomarkers is the understanding of how a test result will alter post-test probabilities and then impact on clin...

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen co...

Objective: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases. Study design and setting: Ped...

Antibody responses to Mycoplasma pneumoniae ( Mp ) correlate with pulmonary Mp clearance. However, Mp -specific IgG antibodies can cross-react with the myelin glycolipid galactocerebroside (GalC) and cause neurologic disorders. We assessed whether anti-glycolipid antibody formation is part of the physiological immune response to Mp . We show that a...

Background: Infectious disease pandemics (IDP) pose a considerable global threat and can disproportionately affect vulnerable populations including children. Pediatric clinical research in pandemics is essential to improve children's healthcare and minimize risks of harm by interventions that lack an adequate evidence base for this population. The...

Otitis media (OM) is one of the most common pediatric infections worldwide, but the complex microbiology associated with OM is poorly understood. Previous studies have shown an association between OM and gastroesophageal reflux (GER) in children. Therefore, in order to bridge the gap in our current understanding of the interaction between GER and O...

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic...

Group authorship list. (DOCX)

Project concept analysis plan. (PDF)

Characteristics by birth cohort. (DOCX)

Comparison by birth cohort. (TIFF)

Standard survival mortality estimates. (DOCX)

Cumulative incidence 10–13 sensitivity. (DOCX)

Selected full models. (DOCX)

Cumulative incidence 10–15 sensitivity. (DOCX)

Crude mortality hazard ratios sensitivity. (DOCX)