Treatment intensity affects immune reconstitution even after childhood cancer not treated with hematopoietic stem cell transplantation.

BACKGROUND: Only a few previous studies examine immune system recovery after completed cancer treatment. AIMS: The aim of this study was to analyze immune reconstitution after childhood cancer therapy in a non-hematopoietic stem cell transplantation setting. METHODS AND RESULTS: We analyzed children (N = 79) who received chemotherapy with/without irradiation for cancer diagnosed between 2014 and 2019 at Turku University Hospital, Finland. We retrospectively collected data on baseline parameters and post-treatment immunological recovery, namely neutrophil and lymphocyte counts, IgG levels, CD19, CD4 and natural killer cell counts. Immunological parameters were followed until their normalization. Treatment intensity was stratified according to the Intensity of Treatment Rating Scale (ITR-3). We analyzed the effects of treatment intensity on normalization of immunological parameters across the entire treatment range. Treatment intensity had a major effect on immune system recovery after completion of treatment. Most patients had normal immunological parameters 1-4 months post-treatment both in high- and low-intensity treatment groups, but patients classified in the high-intensity group had low parameters more often than patients in the low-intensity group. CONCLUSION: Our data suggest a fast recovery of studied immunological parameters after the majority of current pediatric oncologic treatments. Treatment for high-risk acute lymphoblastic leukemia, acute myeloid leukemia, medulloblastoma, and mature B-cell lymphoma was associated with prolonged recovery times for a substantial proportion of cases. High treatment intensity was associated with prolonged immunological recovery.

Genetic polymorphisms of TLR1, TLR2, TLR3 and TLR4 in patients with recurrent or severe infections.

Toll-like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well-studied TLR1-4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C > A, Ser602Ile), TLR2 rs5743708 (2258G > A, Arg753Gln), TLR3 rs3775291 (1234C > T, Leu412Phe) and TLR4 rs4986790 (896A > G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n = 84), severe infections (n = 15) or common variable immunodeficiency (n = 56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45-6.83, p = .004, ap = .016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05-3.12, p = .028, ap = .112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p  ≤ .0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41-6.47; p = .012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections.

ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children.

The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL-33 polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in ST2 and IL-33 were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL-33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL-33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.

Finnish paediatric study found a low incidence of bacterial meningitis from 2011 to 2018 but a substantial proportion of nosocomial meningitis.

AIM: This study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM). METHODS: The medical records of patients under 16 years of age, treated by Turku University Hospital, Finland, from 2011 to 2018, were screened for meningitis using the International Classification of Diseases, Tenth Revision codes. Patients were included if bacteria were detected in cerebrospinal fluid (CSF) or other predefined laboratory variables indicated BM, despite CSF testing negative for bacteria. The Glasgow Outcome Scale (GOS) was used to determine outcomes. RESULTS: We identified 37 children with BM: 22 infants aged 0-89 days and 15 children aged 90 days to 15 years. The overall incidence was approximately 5.7/100 000/year. Nosocomial meningitis was documented in 51%. Bacterial growth was detected in the CSF or blood cultures of the majority of patients (57%). Escherichia coli (14%), group B streptococcus (11%) and Streptococcus pneumoniae (8%) were the most common pathogens. There were 14% of patients with unfavourable outcomes, namely GOS scores of 1-4, but no deaths. CONCLUSION: The incidence of paediatric BM was low during the study period, but the proportion of nosocomial meningitis was substantial. The frequency of unfavourable long-term outcomes was relatively low.

Investigating the role of relationship satisfaction and paternal psychological distress during pregnancy on offspring health in early life.

BACKGROUND: The research on the role of father in the foetal programming of health and behaviour has received increasing attention. However, the influences of paternal depressive symptoms and couple relationship satisfaction during pregnancy - potentially mediated via maternal well-being - on the offspring's risk of infections in early life is still seldom assessed. AIMS: The aim was to investigate if paternal psychological distress during pregnancy is associated with elevated risk of recurrent respiratory infections (RRIs) for offspring at 12 months of age, and whether maternal distress mediates the association between paternal distress and offspring RRIs. METHOD: The study population was drawn from the nested case-control cohort of the FinnBrain Birth Cohort Study. Children with RRIs (n = 50) were identified by maternal reports at the age of 12 months, whereas mothers did not report RRIs for the comparison group (n = 716). Parental depressive symptoms were measured with the Edinburgh Postnatal Depression Scale and couple relationship satisfaction was measured with the Revised Dyadic Adjustment Scale. RESULTS: The association between paternal depressive symptoms during pregnancy and offspring RRIs was mediated by maternal prenatal depressive symptoms. Additionally, paternal poorer relationship satisfaction was associated with child RRIs independently of maternal distress. CONCLUSIONS: The results suggest different pathways through which paternal distress during pregnancy may contribute to elevated risk of offspring RRIs, and more research is needed to study their underlying mechanisms. Paternal distress and couple relationship satisfaction during pregnancy should be assessed and screened as a contributor to offspring health.

Coronavirus spike protein-specific antibodies indicate frequent infections and reinfections in infancy and among BNT162b2-vaccinated healthcare workers.

The prevalence of seasonal human coronavirus (HCoV) infections in early childhood and adults has not been well analyzed in longitudinal serological studies. Here we analyzed the changes in HCoV (229E, HKU1, NL63, OC43, MERS, and SARS-CoV-2) spike-specific antibody levels in follow-up serum specimens of 140 children at the age of 1, 2, and 3 years, and of 113 healthcare workers vaccinated for Covid-19 with BNT162b2-vaccine. IgG antibody levels against six recombinant HCoV spike subunit 1 (S1) proteins were measured by enzyme immunoassay. We show that by the age of three years the cumulative seropositivity for seasonal HCoVs increased to 38-81% depending on virus type. BNT162b2 vaccinations increased anti-SARS-CoV-2 S1 antibodies, but no increase in seasonal coronavirus antibodies associated with vaccinations. In healthcare workers (HCWs), during a 1-year follow-up, diagnostic antibody rises were seen in 5, 4 and 14% of the cases against 229E, NL63 and OC43 viruses, respectively, correlating well with the circulating HCoVs. In 6% of the HCWs, a diagnostic antibody rise was seen against S1 of HKU1, however, these rises coincided with anti-OC43 S1 antibody rises. Rabbit and guinea pig immune sera against HCoV S1 proteins indicated immunological cross-reactivity within alpha-CoV (229E and NL63) and beta-CoV (HKU1 and OC43) genera.

Enterovirus D68 Outbreak in Children, Finland, August-September 2022.

We observed an intense enterovirus D68 outbreak in children in southwest Finland in August-September 2022. We confirmed enterovirus D68 infection in 56 children hospitalized for respiratory illnesses and in 1 child with encephalitis but were not able to test all suspected patients. Continuing surveillance for enterovirus D68 is needed.

Biomarkers of viral and bacterial infection in rhinovirus pneumonia.

Background: Rhinovirus (RV) is often detected in children hospitalized with pneumonia, but the role of RV in causing pneumonia is still unclear. Methods: White blood cell count, C-reactive protein, procalcitonin, and myxovirus resistance protein A (MxA) levels were determined from blood samples in children (n = 24) hospitalized with radiologically verified pneumonia. Respiratory viruses were identified from nasal swabs by using reverse transcription polymerase chain reaction assays. Among RV-positive children, the cycle threshold value, RV subtyping by sequence analysis, and the clearance of RV by weekly nasal swabs were determined. RV-positive children with pneumonia were compared to other virus-positive children with pneumonia, and to children (n = 13) with RV-positive upper respiratory tract infection from a separate earlier study. Results: RV was detected in 6 children and other viruses in 10 children with pneumonia (viral co-detections excluded). All RV-positive children with pneumonia had high white blood cell counts, plasma C-reactive protein or procalcitonin levels, or alveolar changes in chest radiograph strongly indicating bacterial infection. The median cycle threshold value for RV was low (23.2) indicating a high RV load, and a rapid clearance of RV was observed in all. Blood level of viral biomarker MxA was lower among RV-positive children with pneumonia (median 100 µg/L) than among other virus-positive children with pneumonia (median 495 µg/L, p = 0.034) or children with RV-positive upper respiratory tract infection (median 620 µg/L, p = 0.011). Conclusions: Our observations suggest a true viral-bacterial coinfection in RV-positive pneumonia. Low MxA levels in RV-associated pneumonia need further studies.

Diagnostic Performance and Tolerability of Saliva and Nasopharyngeal Swab Specimens in the Detection of SARS-CoV-2 by RT-PCR.

Saliva is a promising alternative for a nasopharyngeal swab (NPS) in specimen collection to detect SARS-CoV-2. We compared the diagnostic performance and tolerability of saliva collection versus NPS in a clinical setting. Paired NPS and saliva specimens were collected sequentially from participants (n = 250) at the Turku University Hospital drive-in coronavirus testing station in the spring of 2022, with Omicron BA.2 as the dominant SARS-CoV-2 variant. Discomfort and preference for the sampling method were assessed. The specimens were analyzed for SARS-CoV-2 using real-time multiplex reverse transcriptase PCR (RT-PCR) with a laboratory-developed test (LDT) and two commercial kits (PerkinElmer SARS-CoV-2 and PerkinElmer SARS-CoV-2 Plus) for several target genes. Among the 250 participants, 246 had respiratory symptoms. With LDT, SARS-CoV-2 was detected in 135 and 134 participants from NPS and saliva, respectively. Of the 250 specimens, 11 gave a discordant outcome, resulting in excellent agreement between the specimen types (Cohen's kappa coefficient of 0.911; P = 0.763). The cycle threshold (CT) values of LDT and commercial kit target genes were significantly lower from NPS than from saliva. A total of 172 (69%) participants assessed saliva sampling as more tolerable than NPS (P < 0.0001). Our findings present saliva as an applicable alternative for SARS-CoV-2 diagnostics. However, the lower CT values obtained from NPS indicate that NPS may be a slightly more sensitive specimen type. Participants preferred saliva sampling, although delivering an adequate volume of saliva was challenging for some participants. IMPORTANCE The extensive testing of SARS-CoV-2 is vital in controlling the spread of COVID-19. The reference standard for specimen collection is a nasopharyngeal swab (NPS). However, the discomfort of NPS sampling, the risk of nosocomial infections, and global material shortages have accelerated the development of alternative testing methods. Our study demonstrates that patients tolerate saliva sampling better than NPS. Of importance, although the RT-PCR qualitative test results seem to correspond between NPS and saliva, we show significantly lower CT values for NPS, compared to saliva, thus contradicting the suggested superiority of the saliva specimen over NPS in the detection of the Omicron variants of SARS-CoV-2. Future research is still required to enable individual planning for specimen collection and to determine the effects of different SARS-CoV-2 variants on the sensitivity of the saliva matrix.

Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.

BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season. METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses. RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile). CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.

Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children.

BACKGROUND: Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear. METHODS: We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies. RESULTS: The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses. CONCLUSIONS: Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575.

Association of Toll-like receptor 2 rs111200466 polymorphism with low serum levels of IL-33 in early childhood.

TLR2 is one of 10 human TLRs, which plays an important role in the recognition of pathogens and activation of the innate immunity via NF-κB pathway. NF-κB activation induces the expression of various pro-inflammatory genes. This study examines the effect of TLR2 polymorphisms on the production of blood pro-inflammatory cytokines in healthy Finnish children. One hundred forty-six children who participated in a prospective observational birth cohort study in Turku, Finland, were included. DNA samples were analysed by PCR-based sequencing for two common TLR2 polymorphisms (rs5743708 Arg753Gln; rs111200466-196 to -174del). Serum concentrations of IL-33, IL-31, IL-17A and IL-17F were measured by multiplex immunoassay and sST2 by ELISA in children at the age of 13 months. Children with variant type of TLR2 rs111200466 (ins/del or del/del) had significantly lower level of serum IL-33 (median, 0.00 pg/mL; IQR 0.00-17.60) than those with ins/ins type of TLR2 (19.81 pg/mL; IQR 0.00-51.78) (p = 0.0001). Almost all study subjects had serum concentrations of IL-17A, IL-17F and IL-31 below the detection limit and therefore not included in the final analyses. No differences in levels of above four cytokines and sST2 were found between TLR2 rs5743708 genotypes (GG and GA). Our results indicated that the TLR2 rs111200466 deletion was associated with a low level of serum IL-33, suggesting that the polymorphism may impair the production of IL-33.

Influence of Respiratory Tract Infections on Vocabulary Growth in Relation to Child's Sex: The STEPS Study.

Common health issues have been less examined in studies of early language development, particularly in relation to the child's sex. Respiratory tract infections, often complicated by acute otitis media, are common in children during the first years of life, when early vocabulary development takes place. The present study, conducted in Finland, aimed to investigate whether possible associations between recurrent respiratory tract infections, background factors, and vocabulary growth differ in boys and girls aged 13 to 24 months. The participants (N = 462, 248 boys and 214 girls) were followed for respiratory tract infections and acute otitis media from 0 to 23 months of age. The parents completed daily symptom diaries of respiratory symptoms, physician visits, and diagnoses. The expressive vocabulary was measured with parental reports. We found that recurrent respiratory tract infections were not associated with slower vocabulary development in boys or girls. In fact, boys with recurrent respiratory tract infections had more vocabulary growth during the second year than boys who were less sick. We found that vocabulary growth was associated differently with respiratory tract infections and background factors as a function of the child's sex. The vocabulary growth of boys seems to be more influenced by environmental factors than that of girls.

Detailed prenatal and postnatal MRI findings and clinical analysis of RAF1 in Noonan syndrome.

Noonan syndrome is a genetically heterogeneous developmental disorder, which usually includes findings such as short stature, facial dysmorphia, cardiac abnormalities and a varying degree of intellectual disability. We present a unique case of a rare variant of Noonan syndrome in a very preterm female infant born at 28 + 4 gestational weeks, with abnormal radiological findings visible at fetal magnetic resonance imaging (MRI) and evolution of the brain lesions during infancy.

Association of human myxovirus resistance protein A with severity of COVID-19.

BACKGROUND: In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients. METHODS: All 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization. RESULTS: Higher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11-46.58; p = 0.004) in patients with MxA between 400 µg/L and 799 µg/L (p = 0.004) and 20.08 (95%CI 4.51-89.44; p < 0.001) in patients with MxA ≥ 800 µg/L in comparison with patients with initial MxA < 400 µg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001). CONCLUSIONS: Higher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease.

Detection of group A streptococcus in children with confirmed viral pharyngitis and antiviral host response.

Our aim was to study the detection of group A streptococcus (GAS) with different diagnostic methods in paediatric pharyngitis patients with and without a confirmed viral infection. In this prospective observational study, throat swabs and blood samples were collected from children (age 1-16 years) presenting to the emergency department with febrile pharyngitis. A confirmed viral infection was defined as a positive virus diagnostic test (nucleic acid amplification test [NAAT] and/or serology) together with an antiviral immune response of the host demonstrated by elevated (≥ 175 µg/L) myxovirus resistance protein A (MxA) blood concentration. Testing for GAS was performed by a throat culture, by 2 rapid antigen detection tests (StrepTop and mariPOC) and by 2 NAATs (Simplexa and Illumigene). Altogether, 83 children were recruited of whom 48 had samples available for GAS testing. Confirmed viral infection was diagnosed in 30/48 (63%) children with febrile pharyngitis. Enteroviruses 11/30 (37%), adenoviruses 9/30 (30%) and rhinoviruses 9/30 (30%) were the most common viruses detected. GAS was detected by throat culture in 5/30 (17%) with and in 6/18 (33%) patients without a confirmed viral infection. Respectively, GAS was detected in 4/30 (13%) and 6/18 (33%) by StrepTop, 13/30 (43%) and 10/18 (56%) by mariPOC, 6/30 (20%) and 9/18 (50%) by Simplexa, and 5/30 (17%) and 6/18 (30%) patients by Illumigene. CONCLUSION: GAS was frequently detected also in paediatric pharyngitis patients with a confirmed viral infection. The presence of antiviral host response and increased GAS detection by sensitive methods suggest incidental throat carriage of GAS in viral pharyngitis. WHAT IS KNOWN: •The frequency and significance of GAS-virus co-detection are poorly characterised in children with pharyngitis. •Detection of a virus and the antiviral host response likely indicates symptomatic infection. WHAT IS NEW: •Group A streptococcus (GAS) was detected in 17-43% of the children with confirmed viral pharyngitis depending on the GAS diagnostic method. •Our results emphasize the risk of detecting and treating incidental pharyngeal carriage of GAS in children with viral pharyngitis.

Neuroimaging and neurological outcome of children with acute encephalitis.

AIM: To investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis. METHOD: Children with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years-11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re-evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short-term (<3 months from discharge) follow-up, and at long-term (>1 year from discharge) follow-up was assessed from medical records using the Glasgow Outcome Scale. RESULTS: Long-term recovery was poor in 24 of 82 (29%) children with follow-up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re-evaluation from 74 of 82 patients with follow-up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery. INTERPRETATION: The risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings. WHAT THIS PAPER ADDS: Poor long-term recovery was found in 29% of children with encephalitis. Severe disability measured by Glasgow Outcome Scale was found in 8%. The most severe neuroimaging findings were a risk factor for severe acute illness and poor long-term recovery.

Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children - The TREND study.

OBJECTIVE: Discriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses. METHODS: Children with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls. RESULTS: MxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 µg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78-99%) sensitivity and 100% (95% CI: 51-100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 µg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 µg/l, interquartile range: 679 to 2489). DISCUSSION: MxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.

Parental socioeconomic and psychological determinants of the 2009 pandemic influenza A(H1N1) vaccine uptake in children.

BACKGROUND: Before COVID-19, the previous pandemic was caused by influenza A(H1N1)pdm09 virus in 2009. Identification of factors behind parental decisions to have their child vaccinated against pandemic influenza could be helpful in planning of other pandemic vaccination programmes. We investigated the association of parental socioeconomic and psychosocial factors with uptake of the pandemic influenza vaccine in children in 2009-2010. METHODS: This study was conducted within a prospective birth-cohort study (STEPS Study), where children born in 2008-2010 are followed from pregnancy to adulthood. Demographic and socioeconomic factors of parents were collected through questionnaires and vaccination data from electronic registers. Before and after the birth of the child, the mother's and father's individual and relational psychosocial well-being, i.e. depressive symptoms, dissatisfaction with the relationship, experienced social and emotional loneliness, and maternal anxiety during pregnancy, were measured by validated questionnaires (BDI-II, RDAS, PRAQ, and UCLA). RESULTS: Of 1020 children aged 6-20 months at the beginning of pandemic influenza vaccinations, 820 (80%) received and 200 (20%) did not receive the vaccine against influenza A(H1N1)pdm09. All measures of parents' psychosocial well-being were similar between vaccinated and non-vaccinated children. Children of younger mothers had a higher risk of not receiving the influenza A(H1N1)pdm09 vaccine than children of older mothers (OR 2.59, 95% CI 1.52-4.43, for mothers < 27.7 years compared to ≥ 33.6 years of age). Children of mothers with lower educational level had an increased risk of not receiving the vaccine (OR 1.46, 95% CI 1.00-2.14). CONCLUSIONS: Mother's younger age and lower education level were associated with an increased risk for the child not to receive the 2009 pandemic influenza vaccine, but individual or relational psychosocial well-being of parents was not associated with children's vaccination. Our findings suggest that young and poorly educated mothers should receive targeted support in order to promote children's vaccinations during a pandemic.