Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content
, regulating both physiological intestinal functions such as nutrient absorption and motility
..., and brain-wired feeding behaviour
. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology
. Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations. We find that the gut microbiome modulates gut-extrinsic sympathetic neurons: microbiota depletion leads to increased expression of the neuronal transcription factor cFos, and colonization of germ-free mice with bacteria that produce short-chain fatty acids suppresses cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling and anterograde tracing identify a subset of distal intestine-projecting vagal neurons that are positioned to have an afferent role in microbiota-mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identifies brainstem sensory nuclei that are activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota-dependent control of gut-extrinsic sympathetic activation through a gut-brain circuit.
The risk factors in pediatric influenza immediately before the COVID-19 era are not well understood. This study aims to evaluate the risk factors for hospitalization in pediatric influenza A and B ...for the recent seasons.
Children with a fever of ≥38 °C and laboratory-confirmed influenza at 20 hospitals in outpatient settings in Japan in the 2013/14 to 2019/20 seasons were retrospectively reviewed. Possible risk factors, including gender, age, comorbidities, nursery school or kindergarten attendance, earlier diagnosis, no immunization, lower regional temperature, earlier season, and period of onset, were evaluated using binary logistic regression methods.
A total of 13,040 (type A, 8861; B, 4179) children were evaluated. Significant risk factors (p < 0.05) in multivariate analyses were young age, lower regional temperature, earlier season, respiratory illness (adjusted odds ratio aOR:2.76, 95% confidence interval CI:1.84–4.13), abnormal behavior and/or unusual speech (aOR:2.78, 95% CI:1.61–4.80), and seizures at onset (aOR:16.8, 95% CI:12.1–23.3) for influenza A; and young age, lower regional temperature, respiratory illness (aOR:1.99, 95% CI:1.00–3.95), history of febrile seizures (aOR:1.73, 95% CI:1.01–2.99), and seizures at onset (aOR:9.74, 95% CI:5.44–17.4) for influenza B.
In addition to previously known factors, including young age, seizures, and respiratory illness, abnormal behavior and/or unusual speech and lower regional temperature are new factors. Negative immunization status was not a risk factor for hospitalization. A better understanding of risk factors may help improve the determination of indications for hospitalization during the future co-circulation of influenza and COVID-19.
Abstract Background Coagulase-negative Staphylococcus (CoNS) is the predominant cause of catheter-related bloodstream infections (CRBSI). Infants in neonatal intensive care units (NICU) often suffer ...from CoNS CRBSI, which are often refractory to treatment. Objectives We sought to evaluate risk factors for developing persistent bacteremia due to CoNS CRBSI in infants, in order to identify those who require early aggressive management. Methods We conducted a retrospective case-control study of infants in the NICU who developed CRBSI due to CoNS. Patient demographics, condition and management of CRBSI were compared between those with persistent and non-persistent bacteremia. Furthermore, prognosis of infants in the NICU after CoNS CRBSI was evaluated. Results Seventy six episodes of CRBSI, including 17 persistent bacteremia and 59 non-persistent bacteremia, were analyzed. In univariate analyses, persistent bacteremia was significantly associated with corrected age equivalent to gestational age of 22-28 weeks at onset of CRBSI Odds ratio (OR)=4.33; P = 0.04, platelet count <100,000/μL (OR=11.5; P <0.001), use of vasopressor (OR=5.38; P =0.003), and delayed CVC removal (OR=6.25; P =0.003). In multivariate analysis, persistent bacteremia was significantly associated with platelet count <100,000/μL (OR=7.80; P =0.007), and delayed CVC removal (OR=5.07; P =0.03). Infants with persistent bacteremia tended to have a lower survival rate after CoNS CRBSI, however this was not statistically significant ( P =0.21). Conclusions Early CVC removal should be considered for the treatment of CRBSI due to CoNS in infants with platelet counts of less than 100,000/μL.
Abstract
Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions
1–3
. However, the players and mechanisms that underlie ...protease regulation in the intestinal lumen have remained unclear. Here we show that
Paraprevotella
strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically,
Paraprevotella
recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis.
Paraprevotella
colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against
Citrobacter rodentium
. Moreover,
Paraprevotella
colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells
4,5
. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.
Urinary tract infection (UTI) is one of the most common bacterial infections in children. The symptoms of UTI in young children are nonspecific, therefore urine should be examined whenever UTI cannot ...be ruled out. In clinical settings, however, collecting urine from children who are not toilet trained is sometimes difficult, presenting a challenge in UTI management. Here, we developed a "diaper UTI test", which enables the quick detection of pyuria in ordinary diapers, and investigated its sensitivity and specificity in a clinical study. The diaper UTI test is based on a leukocyte esterase reaction. Reagent was prepared in liquid form so that it can be absorbed by disposable diapers, where it will produce a violet color in the presence of pyuria. For the clinical study, we enrolled children younger than 3 years with potential UTI who underwent bladder catheterization for urine culture and urinalysis. Of the 65 children included, 21 were diagnosed with UTI. The sensitivity and specificity of the diaper UTI test were 90.5% (95% CI 69.6-98.8) and 93.2% (95% CI 81.3-98.6), respectively. Because of its convenience and good sensitivity, the diaper UTI test may be useful in the screening of pediatric UTI.
Bloodstream infection (BSI) is a major cause of morbidity and mortality after pediatric liver transplantation (LT). However, most studies have focused on BSI occurring within a few months after LT. ...In this study, we evaluated the characteristics of BSI occurring beyond 6 months after pediatric LT.
We conducted a retrospective cohort study at a pediatric LT center in Japan from November 2005 to March 2016. We evaluated the causative organisms and site of late-onset BSI in children ≤ 18 years of age. The risk factors for developing late-onset BSI and the associations of late-onset BSI with long-term outcomes were also evaluated.
Three hundred forty cases of LT were evaluated. Thirty-eight BSI developed in 29 (9%) LT recipients. There were 42 organisms (nine Gram-positive cocci, 33 Gram-negative rods) isolated from the blood cultures of recipients with late-onset BSI. The most frequent sites of late-onset BSI was intraabdominal infection (18/38; 47%). There were also 14 (39%) episodes with no apparent focus. In multivariate analysis, a prolonged operative time > 12 hours (odds ratio OR = 3.55; P = 0.04) and biliary stenosis (OR = 4.60; P = 0.006) were independent risk factors for developing late-onset BSI. Late-onset BSI was associated with increased retransplantation rate (P = 0.04) and mortality (P < 0.001).
Late-onset BSI developed in 9% of recipients after pediatric LT. Gram-negative rods accounted for the majority of late-onset BSI as a consequence of abdominal infection, but the focus was often unclear. Prolonged operative time at LT and biliary stenosis were independent risk factors for developing late-onset BSI.
Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan. The overall incidence of bacterial meningitis decreased thereafter. ...Streptococcus agalactiae has become the main organism.
The purpose of the present study was to investigate the incidence rate per 1000 admissions of bacterial meningitis and the change in causative organisms in subsequent years.
A cross-sectional, multicenter, non-interventional retrospective study regarding pediatric bacterial meningitis was conducted in Japan in 2019. We analyzed the epidemiological and clinical data for 2016–2018, and compared the information obtained in our previous nationwide survey database. We also investigated the risk factors for disease outcome.
In the 2016–2018 surveys, 197 patients from 153 hospitals from all prefectures were evaluated. S. agalactiae (0–3 months, 39%), Streptococcus pneumoniae (2–112 months, 20%), and E. coli (0–136 months, 13%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.00 to 1.68 in 2000–2010 to 0.38 in 2013–2015, bu remained stable thereafter (0.35–0.40 in 2016–2018). Only one case with Neisseria meningitidis was reported. Nine cases with death were reported, including four cases with S. agalactiae. Risk factors for death and sequelae were consciousness disturbance, duration of convulsion, low CSF glucose levels, and disuse of dexamethasone (p < 0.05).
The incidence in pediatric bacterial meningitis remained low, and S. agalactiae remains the most common cause of bacterial meningitis in Japan since 2012. S. pneumoniae is the most common cause after 3 months of age.
•Flu vaccine effectiveness for children was analyzed for 2013/14 to 2019/20.•Recent inactivated flu vaccine is effective in children and infants for flu A.•Vaccine effectiveness was highest among 1 ...to 2 year olds for flu A and flu B.•Flu vaccine effectively prevents flu A hospital admission in children aged 1–12.
We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6–11 months) and older (6–15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups.
The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6–11 months, 1–2, 3–5, 6–12, and 13–15 years old) with adjustments including influenza seasons.
A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% 95% confidence interval (CI), 41–47, 63% 95 %CI, 51–72, and 37% 95 %CI, 32–42, respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% 95 %CI, 55–65 and 52% 95 %CI, 41–61, respectively). Analysis for the 2020/21 season was not performed because no cases were reported.
This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.
•Both one- and two-doses regimens of inactivated flu vac are effective for children.•Both regimens reduced cases involving hospitalization due to influenza A.•The two-dose regimen was more effective ...against influenza B in some seasons.
We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.
VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.
In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 95% CI, 0.505–0.621, 0.550 95% CI, 0.516–0.586), 0.549 95% CI, 0.517–0.583, and 1.014 95% CI, 0.907–1.135, for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.
Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.
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