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.

Respiratory viral infections - impact on sport and exercise medicine.

Respiratory viruses are the most frequent causative agents of disease in humans and thus also in elite athletes. The COVID-19 pandemic has recently emphasized the entire spectrum of respiratory tract infections worldwide. Understanding the basic elements of respiratory viral infections is a fundamental requirement from the perspective of etiological diagnostics, treatment, and prevention strategy planning, as well as resource allocation.

Non-SARS-CoV-2 Respiratory Viruses in Athletes at Major Winter Sport Events, 2021 and 2022.

We performed prospective studies on respiratory viral infections among Team Finland participants during the 2021 Oberstdorf World Ski Championships and the 2022 Beijing Olympic Games. We enrolled 73 athletes and 110 staff members. Compared with similar studies we conducted before the COVID-19 pandemic, illnesses and virus detections dropped by 10-fold.

Review of the clinical significance of respiratory virus infections in newborn infants.

UNLABELLED: Respiratory viruses have been recognised as causative agents for a wide spectrum of clinical manifestations and severe respiratory compromise in neonates during birth hospitalisation. Early-life respiratory virus infections have also been shown to be associated with adverse long-term consequences. CONCLUSION: Preventing virus infections by intensifying hygiene measures and cohorting infected infants should be a major goal for neonatal intensive care units, as well as more common use of virus diagnostics. Active virus surveillance and long-term follow-up are needed to ascertain the causality and exact underlying mechanisms for adverse long-term consequences.

Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial.

BACKGROUND: Simple and safe strategies for the prevention of viral respiratory tract infections (RTIs) are needed. OBJECTIVE: We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants. METHODS: In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no. NCT00167700), 94 preterm infants (gestational age, ≥32 + 0 and ≤36 + 6 weeks; birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome was the incidence of clinically defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing. Secondary outcomes were the severity and duration of RTIs. RESULTS: A significantly lower incidence of RTIs was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12-0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared with those receiving placebo. Also, the incidence of rhinovirus-induced episodes, which comprised 80% of all RTI episodes, was found to be significantly lower in the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49; 95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No differences emerged among the study groups in rhinovirus RNA load during infections, duration of rhinovirus RNA shedding, duration or severity of rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants. CONCLUSIONS: Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections.

[Neonatal sepsis]. / Vastasyntyneen sepsis.

Many newborns are exposed to diagnostic or treatment procedures due to a suspicion of sepsis. Since non-specific signs of neonatal sepsis can quickly proceed to a life-threatening condition, it is essential to have a low threshold to diagnostic procedures and to provide antimicrobial therapy while waiting for the test results. After sepsis has been ruled out, antimicrobial therapy should be discontinued without delay. Good clinical practice includes avoiding unnecessarily broad-spectrum antibiotics. The future challenge is to develop a sensitive and specific marker for early detection of the disease and for avoiding unnecessary antibiotics, hospital care days and mother-infant separation.

[Neonatal virus infections]. / Vastasyntyneen virusinfektiot.

At birth the immune system of a neonate is immature and viruses can cause severe infections. Since the signs and symptoms of postnatal viral diseases can be identical to those in bacterial infections, viral diseases are often treated with antibiotics. Any infant with signs of serious infections, in whom no bacteria are found, should be suspected for a viral infection. Prevention of transmission of viruses and cohorting of infected infants should be practiced in NICUs. Since postnatal viral infections can have a long-term impact on the health in a child, all effective preventive and curative interventions should be utilized.

Contraction of Respiratory Viral Infection During air Travel: An Under-Recognized Health Risk for Athletes.

Air travel has an important role in the spread of viral acute respiratory infections (ARIs). Aircraft offer an ideal setting for the transmission of ARI because of a closed environment, crowded conditions, and close-contact setting. Numerous studies have shown that influenza and COVID-19 spread readily in an aircraft with one virus-positive symptomatic or asymptomatic index case. The numbers of secondary cases differ markedly in different studies most probably because of the wide variation of the infectiousness of the infector as well as the susceptibility of the infectees. The primary risk factor is sitting within two rows of an infectious passenger. Elite athletes travel frequently and are thus prone to contracting an ARI during travel. It is anecdotally known in the sport and exercise medicine community that athletes often contract ARI during air travel. The degree to which athletes are infected in an aircraft by respiratory viruses is unclear. Two recent studies suggest that 8% of Team Finland members traveling to major winter sports events contracted the common cold most probably during air travel. Further prospective clinical studies with viral diagnostics are needed to understand the transmission dynamics and to develop effective and socially acceptable preventive measures during air travel.

Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the impact of early prebiotic and probiotic intervention on preterm infants' well-being, crying, growth, and microbiological programming. STUDY DESIGN: Ninety-four preterm infants (gestational age 32-36 weeks and birth weight >1500 g) randomized to receive prebiotics (mixture of galacto-oligosaccharide and polydextrose 1:1), probiotics (Lactobacillus rhamnosus GG), or placebo during the first 2 months of life were followed up for 1 year. Infants were categorized based on the extent of crying and irritability during the first 2 months of life, and their gut microbiota was investigated by fluorescence in situ hybridization (n = 66) and quantitative polymerase chain reaction (n = 63). RESULTS: A total of 27 of 94 infants (29%) infants were classified as excessive criers, significantly less frequently in the prebiotic and the probiotic groups than in the placebo group (19% vs 19% vs 47%, respectively; P = .02). The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group (13.9% vs 8.9%, respectively; P = .05). There were no adverse events related to either supplementation. CONCLUSIONS: Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants. This original finding may offer new therapeutic and preventive measures for this common disturbance in early life.

Gross blood in stools of premature neonates, a clinical and microbiological follow-up study.

AIM: To characterize the clinical course and the gut microecology of premature infants with macroscopic gross blood in stools. METHODS: We studied 14 premature infants receiving breast milk supplemented with probiotics, according to our units practice, with macroscopic blood in stools without signs of ileus or systemic infection upon occurrence of the symptom and 14 days later. Controls were matched prospectively by gestational and postnatal age and type of feeding. Gut microbiota composition was analysed by quantitative real-time polymerase chain reaction (qPCR), and the presence of enteric viruses in the stools was assayed by PCR and by reverse transcription reaction followed by PCR (RT-PCR). RESULTS: The symptom was transient, benign and self-limiting and none of the background factors explained it. No enteric viruses were detected, and the bacterial analyses showed no statistically significant differences between the infants with or without gross blood in stools. The characterization of the gut microbiota revealed low bacterial diversity. CONCLUSION: Gross blood in the stools of premature infants without other clinical signs of infection can be an innocuous and self-limiting symptom. This cohort of preterm infants receiving breast milk supplemented with probiotics showed no alterations in gut microecology to be associated with the symptom.

Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial.

The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.

Respiratory Viral Infections in Athletes: Many Unanswered Questions.

Upper respiratory tract infections ("common cold") are the most common acute illnesses in elite athletes. Numerous studies on exercise immunology have proposed that intense exercise may increase susceptibility to respiratory infections. Virological data to support that view are sparse, and several fundamental questions remain. Immunity to respiratory viral infections is highly complex, and there is a lack of evidence that minor short- or long-term alterations in immunity in elite athletes have clinical implications. The degree to which athletes are infected by respiratory viruses is unclear. During major sport events, athletes are at an increased risk of symptomatic infections caused by the same viruses as those in the general population. The symptoms are usually mild and self-limiting. It is anecdotally known that athletes commonly exercise and compete while having a respiratory viral infection; there are no virological studies to suggest that such activity would affect either the illness or the performance. The risk of myocarditis exists. Which simple mitigation procedures are crucial for effective control of seasonal respiratory viral infections is not known.

Gut Microbiota and Serum Metabolome in Elite Cross-Country Skiers: A Controlled Study.

Exercise has been shown to affect gut the microbiome and metabolic health, with athletes typically displaying a higher microbial diversity. However, research on the gut microbiota and systemic metabolism in elite athletes remains scarce. In this study, we compared the gut microbiota profiles and serum metabolome of national team cross-country skiers at the end of an exhausting training and competitive season to those of normally physically-active controls. The gut microbiota were analyzed using 16S rRNA amplicon sequencing. Serum metabolites were analyzed using nuclear magnetic resonance. Phylogenetic diversity and the abundance of several mucin-degrading gut microbial taxa, including Akkermansia, were lower in the athletes. The athletes had a healthier serum lipid profile than the controls, which was only partly explained by body mass index. Butyricicoccus associated positively with HDL cholesterol, HDL2 cholesterol and HDL particle size. The Ruminococcus torques group was less abundant in the athlete group and positively associated with total cholesterol and VLDL and LDL particles. We found the healthier lipid profile of elite athletes to co-occur with known health-beneficial gut microbes. Further studies should elucidate these links and whether athletes are prone to mucin depletion related microbial changes during the competitive season.

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries.

Background: Immunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination. Aim: We studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries. Materials and methods: From a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups. Results: Geometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year. Conclusions: An aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.

Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age.

OBJECTIVE: The aim of the study was to characterize early nutritional and microbiological environments (maternal colostrum adiponectin concentration and early gut microbiota composition) in children subsequently becoming normal weight versus overweight. PATIENTS AND METHODS: Fifteen overweight children at 10 years of age were identified from an ongoing prospective nutrition, allergy, mucosal immunology and intestinal microbiota project. Normal-weight children (n = 15), matched for sex, gestational age and body mass index at birth, mode of delivery, probiotic intervention, and duration of breast-feeding, were identified from the same cohort as controls. To characterize the early dietary environment we analyzed the adiponectin concentration in the maternal colostrum. With an aim to assess the initial microbiological environment, we analyzed the gut microbiota composition by fluorescent in situ hybridization in these children at the age of 3 months. Additionally, putative early markers of low-grade inflammation, such as serum-soluble innate microbial receptor sCD14, were analyzed at the age of 3 months. RESULTS: The colostrum adiponectin concentration was significantly higher in mothers whose children were normal weight than in those whose children were overweight at the age of 10 years (P = 0.001). In parallel, the normal-weight children had significantly higher sCD14 concentrations in the serum (P = 0.049) and tended to have higher bifidobacterial numbers in the gut microbiota (P = 0.087) at the age of 3 months. CONCLUSIONS: The results of the present study suggest that early dietary and gut microbiological environments have a more complex effect on the metabolic programming of a child than previously anticipated.

Increased risk of respiratory viral infections in elite athletes: A controlled study.

BACKGROUND: Respiratory symptoms are commonly recognised in elite athletes. The occurrence, etiology and clinical presentation of the illnesses in athletes is unclear. METHODS: We performed a prospective controlled study of respiratory viral infections in Team Finland during Nordic World Ski Championships 2019. There were 26 athletes and 36 staff members. Nasal swabs were taken at the onset of a symptom and on days 1, 7, and 13 during the follow-up of 14 days. Respiratory viruses were searched for by 3 different molecular multiplex tests. Fifty-two matched control subjects were studied in Finland during the same period. RESULTS: Ten out of 26 (38%) athletes, 6 out of 36 (17%) staff, and 3 out of 52 (6%) control subjects experienced symptoms of respiratory infection (p = 0.0013). The relative risks for acquiring symptomatic infection were 6.7 (95% confidence interval [CI], 2.1-21.0) of athletes and 2.9 (95% CI, 0.84-10.0) of the staff as compared to the controls. Asymptomatic infections were identified in 8%, 22%, and 19%, respectively (p = 0.30). The etiology of respiratory infections was detected in 84% of the cases. CONCLUSION: The athletes had a 7-fold increase in the risk of illness compared to normally exercising control subjects.

Survey of Viral Reactivations in Elite Athletes: A Case-Control Study.

Exercise-induced immune perturbations have been proposed to increase susceptibility to viral infections. We investigated the replication of persisting viruses as indicators of immune function in elite cross-country skiers after ten months of sustained high-performance exercise. The viruses evaluated, nine human herpesviruses (HHVs) and torque teno virus (TTV), are typically restrained in health but replicate actively in immunosuppressed individuals. We collected sera from 27 Finnish elite cross-country skiers at the end of the competition's season and 27 matched controls who perform moderate exercise. We quantified all the HHVs and-TTV via highly sensitive qPCRs. To verify equal past exposures between the groups, we assessed the IgG antibody prevalences toward HHV-4 (Epstein-Barr virus, EBV) and HHV-5 (human cytomegalovirus, HCMV). We found equal TTV DNA prevalences in athletes (63%) and controls (63%) and loads with respective geometric means of 1.7 × 103 and 1.2 × 103 copies/mL of serum. Overall, the copy numbers were low and consistent with those of healthy individuals. Neither of the groups presented with herpesvirus viremia despite similar past exposures to HHVs (seroprevalences of EBV 70% vs. 78% and HCMV 52% vs. 44% in athletes and controls, respectively). We found no evidence of increased replication of persistent viruses in elite athletes, arguing against impaired viral immunity due to high-performance exercise.

Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice.

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.

Responses to an acellular pertussis booster vaccination in children, adolescents, and young and older adults: A collaborative study in Finland, the Netherlands, and the United Kingdom.

BACKGROUND: Pertussis can lead to serious disease and even death in infants. Older adults are more vulnerable to complications as well. In high-income countries, acellular pertussis vaccines are used for priming vaccination. In the administration of booster vaccinations to different age groups and target populations there is a substantial between-country variation. We investigated the effect of age on the response to acellular pertussis booster vaccination in three European countries. METHODS: This phase IV longitudinal intervention study performed in Finland, the Netherlands and the United Kingdom between October 2017 and January 2019 compared the vaccine responses between healthy participants of four age groups: children (7-10y), adolescents (11-15y), young adults (20-34y), and older adults (60-70y). All participants received a three-component acellular pertussis vaccine. Serum IgG and IgA antibody concentrations to pertussis antigens at day 0, 28, and 1 year were measured with a multiplex immunoassay, using pertussis toxin concentrations at day 28 as primary outcome. This trial is registered with ClinicalTrialsRegister.eu (2016-003,678-42). FINDINGS: Children (n = 109), adolescents (n = 121), young adults (n = 74), and older adults (n = 75) showed high IgG antibody concentrations to pertussis toxin at day 28 with GMCs of 147 (95% CI 120-181), 161 (95% CI 132-196), 103 (95% CI 80-133), and 121 IU/ml (95% CI 94-155), respectively. A significant increase in GMCs for vaccine antigens in all age groups by 28 days was found which had decreased by 1 year. Differences in patterns of IgG GMCs at 28 days and 1 year post-vaccination did not have a consistent relationship to age. In contrast, IgA antibodies for all antigens increased with age at all timepoints. INTERPRETATION: Acellular pertussis booster vaccination induces significant serum IgG responses to pertussis antigens across the age range which are not uniformly less in older adults. Acellular boosters could be considered for older adults to reduce the health and economic burden of pertussis.

Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study.

The perinatal nutritional environment impacts upon the health and well-being of mother and child also in the long term. The aim of the present study was to determine the safety and efficacy of perinatal probiotic-supplemented dietary counselling by evaluating pregnancy outcome and fetal and infant growth during the 24 months' follow-up. Altogether, 256 women were randomised at their first trimester of pregnancy into a control and a dietary intervention group. The intervention group received intensive dietary counselling provided by a nutritionist and were further randomised, double-blind to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12; diet/probiotics) or placebo (diet/placebo). Firstly, probiotic intervention reduced the frequency of gestational diabetes mellitus (GDM); 13 % (diet/probiotics) v. 36 % (diet/placebo) and 34 % (control); P = 0.003. Secondly, the safety of this approach was attested by normal duration of pregnancies with no adverse events in mothers or children. No significant differences in prenatal or postnatal growth rates among the study groups were detected. Thirdly, distinctive effects of the two interventions were detected; probiotic intervention reduced the risk of GDM and dietary intervention diminished the risk of larger birth size in affected cases; P = 0.035 for birth weight and P = 0.028 for birth length. The results of the present study show that probiotic-supplemented perinatal dietary counselling could be a safe and cost-effective tool in addressing the metabolic epidemic. In view of the fact that birth size is a risk marker for later obesity, the present results are of significance for public health in demonstrating that this risk is modifiable.