Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator,are associated with a distinctive subtype of acute,necrotizing encephalopathy

PurposeMendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)–associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype.MethodsThis study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy.ResultsAll 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family.ConclusionBiallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.     

Campylobacter spp among Children with acute diarrhea attending Mulago hospital in Kampala - Uganda

Background

Campylobacter infections occur worldwide. A recent study in Kampala, Uganda, found that 87% of broiler chickens had Campylobacter jejuni; these are potential source of human infection. Isolation rate in developing countries is between 5–35%. This study aimed at finding prevalence of children with campylobacter infection among children with acute diarrhea attending Mulago hospital.

Objective

The objective was to establish the proportion of children infected with Campylobacter spp among children with acute diarrhea at Mulago hospital.

Methods

A crossectional study from July to October 2005 was conducted involved 226 children with acute diarrhea. Serial sampling was done a total of 226 stool specimens were obtained and cultured on selective media. Identification was done using biochemical test and susceptibility using standard discs diffusion method.

Results

Campylobacter spp were isolated in 21 (9.3%) of 226 stool specimens analyzed. Campylobacter jejuni 17 (80.9%), Campylobacter lari 2 (9.5%), Campylobacter coli 1 (4.5%) and Campylobacter jejuni/coli 1(4.5%). All Campylobacter isolates were sensitive to erythromycin, and 20% had intermediate resistance to Ampicillin.

Conclusion

Campylobacter spp are prevalent among children with acute diarrhea in Kampala- Uganda. A large multicenter study should be undertaken so that the extent of campylobacter infection in our setting can be established.     

Diarrhoeagenic Escherichia coli isolated from children with acute diarrhoea at Rakai hospital,Southern Uganda

BackgroundDiarrhoeagenic Escherichia coli (DEC) is a leading cause of childhood diarrhoea. This study estimated the prevalence of DEC and DEC pathotypes among children with acute diarrhoea in Southern Uganda.MethodsA cross-sectional study was conducted on 267 children less than 5 years with acute diarrhoea, admitted to Rakai General Hospital in Southern Uganda. Faecal samples were collected from the children and processed for isolation of E. coli. The presence of DEC and the distribution of DEC pathotypes were determined by polymerase chain reaction.ResultsA total of 102 (38.2%, 102/267) children had DEC of various pathotypes – enteroaggregative E. coli (EAEC) (14.2%); enteropathogenic E. coli (EPEC) (6.7%); enterotoxigenic E. coli (ETEC) (6%); enteroinvasive E. coli (EIEC) (7.5%); enterohemorrhagic E. coli (EHEC) (3%); and cell-detaching E. coli (CDEC) (0.75%). The difference in the overall prevalence of DEC was not significant regarding HIV but individually, EAEC and CDEC were associated with HIV-positive status while ETEC was associated with HIV-negative status.ConclusionsDEC is prevalent in children with acute diarrhoea in Southern Uganda and its identification in children should be considered among strategies for combatting childhood diarrhoea in Africa.     

Inhibition of the in vitro growth of plasmodium falciparum by human polymorphonuclear neutrophil leucocytes

Polymorphonuclear neutrophil leucocytes (PMN) from children with acute Plasmodium falciparum malaria significantly inhibited parasite growth in homologous and in non-immune sera. Phagocytosis of schizonts in vitro was observed. PMN from uninfected children and uninfected adults had no effect on parasite growth.     

Viability and Functionality of Cryopreserved Peripheral Blood Mononuclear Cells in Pediatric Dengue

Cryopreserved peripheral blood mononuclear cells (PBMCs) are widely used in studies of dengue. In this disease, elevated frequency of apoptotic PBMCs has been described, and molecules such as soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligands (sTRAIL) are involved. This effect of dengue may affect the efficiency of PBMC cryopreservation. Here, we evaluate the viability (trypan blue dye exclusion and amine-reactive dye staining) and functionality (frequency of gamma interferon [IFN-γ]-producing T cells after polyclonal stimulation) of fresh and cryopreserved PBMCs from children with dengue (in acute and convalescence phases), children with other febrile illnesses, and healthy children as controls. Plasma sTRAIL levels were also evaluated. The frequencies of nonviable PBMCs detected by the two viability assays were positively correlated (r = 0.74; P < 0.0001). Cryopreservation particularly affected the PBMCs of children with dengue, who had a higher frequency of nonviable cells than healthy children and children with other febrile illnesses (P ≤ 0.02), and PBMC viability levels were restored in the convalescent phase. In the acute phase, an increased frequency of CD3⁺ CD8⁺ amine-positive cells was found before cryopreservation (P = 0.01). Except for B cells in the acute phase, cryopreservation usually did not affect the relative frequencies of viable PBMC subpopulations. Dengue infection reduced the frequency of IFN-γ-producing CD3⁺ cells after stimulation compared with healthy controls and convalescent-phase patients (P ≤ 0.003), and plasma sTRAIL correlated with this decreased frequency in dengue (rho = −0.56; P = 0.01). Natural dengue infection in children can affect the viability and functionality of cryopreserved PBMCs.     

A potent antibody-secreting B cell response to Mycoplasma pneumoniae in children with pneumonia

BackgroundMycoplasma pneumoniae is a major pathogen for community-acquired pneumonia and frequently causes outbreaks in children. M. pneumoniae-specific antibody response is detected upon acute infection and the serology is widely used in the clinical setting. Nevertheless, the cellular basis for antigen-specific antibody response to acute M. pneumoniae infection is largely undetermined in children.MethodsHospitalized children with community-acquired pneumonia were enrolled and the infection with M. pneumoniae was confirmed with positive PCR result and negative findings for other pathogens. The M. pneumoniae P1-specific antibody-secreting B cell (ASC) response was examined with the ex vivo enzyme-linked immunosorbent spot assay and the relationships between the ASC frequency and serological level and clinical parameters within M. pneumoniae patients were studied.ResultsA robust M. pneumoniae P1-specific ASC response was detected in the peripheral blood among M. pneumoniae-positive patients. By contrast, no M. pneumoniae-specific ASCs were detected among M. pneumoniae-negative patients. The IgM-secreting B cells are the predominant class and account for over 60% of total circulating M. pneumoniae-specific ASCs in the acute phase of illness. The M. pneumoniae P1-specific ASC frequency significantly correlated with the fever duration, and the IgG ASC frequency significantly correlated with serological titer among patients.ConclusionA rapid and potent elicitation of peripheral M. pneumoniae-specific ASC response to acute infection provides the cellular basis of antigen-specific humoral response and indicates the potential of cell-based diagnostic tool for acute M. pneumoniae infection. Our findings warrant further investigations into functional and molecular aspects of antibody immunity to M. pneumoniae.     

Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

Following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive for Streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.     

Characterization of precipitating antibodies to E. coli O antigen in infants and children with acute pyelonephritis

Precipitating serum antibodies to Escherichia coli O antigens from some infants and children with acute pyelonephritis were studied.     

Recent Decrease in Acute Graft-versus-Host Disease in Children with Leukemia Receiving Unrelated Donor Bone Marrow Transplants

Unrelated donor (URD) bone marrow transplantation (BMT) is an effective treatment for leukemia in children, but its success is threatened by graft-versus-host disease (GVHD) and relapse. In this report, we describe the incidence of and risk factors for GVHD over time in children receiving URD BMT. We analyzed outcomes of 638 myeloablative URD BMTs performed between 1990 and 2003 to treat acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia, or myelodysplastic syndrome MDS, using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. All recipients were under age 18 years and had available high-resolution HLA typing for HLA-A, -B, -C, and -DRB1. Overall, 27% of the recipients developed acute GVHD (aGVHD) grade III-IV; the risk was significantly higher in children receiving T cell–replete grafts compared with those receiving T cell–depleted grafts (odds ratio [OR] = 3.12; 95% confidence interval [CI] = 2.02 to 4.83; P < .0001). Acute GVHD significantly reduced the risk of relapse in children with ALL (OR = 0.34; 95% CI = 0.13 to 0.86; P = .0052), but not in those with AML (OR = 0.58; 95% CI = 0.22 to 2.98; P = .26). The risk of aGVHD was higher in children undergoing transplantation in 1990-1998 (n = 365) compared with those doing so in 1999-2003 (OR = 1.93; 95% CI = 1.27 to 2.91; P = .002). We conclude that outcomes have changed significantly over time, with a reduced risk of aGVHD associated with the more recent transplantations.     

Decreased Antitoxic Activities among Children with Clinical Episodes of Malaria

Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children with clinical symptoms. Concentrations of soluble tumor necrosis factor receptor I and C-reactive protein were associated with levels of parasitemia. We detected antitoxic activities in sera as measured by their capacity to block toxin-induced Limulus amoebocyte lysate (LAL) activation. Symptomatic children had decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum erythrocyte membrane protein 1 and “Pfalhesin” (band #3) peptides, indicating that such IgG antibodies are stimulated by acute disease but are lost rapidly after the disease episode. Half of the children with symptomatic infections had low levels of haptoglobin, suggesting that these children had chronic P. falciparum infections which may have caused symptoms previously. Only a few of the children with asymptomatic P. falciparum infections had high parasite counts, and antitoxic immunity in the absence of antiparasite immunity appears to be rare among children in this community.     

Disseminated nongranulomatous Mycobacterium avium osteomyelitis

A 17 month old black girl had multiple, rapidly progressive osteolytic lesions, cervical lymphadenopathy, fever, and weight loss clinically compatible with disseminated malignant disease. Histologically the bone lesions were characteristic of acute nongranulomatous osteomyelitis with a few acid fast organisms. Mycobacterium avium was cultured. Immunologic evaluation showed an intact response to the infection. Disseminated Mycobacterium avium infection may occur in immunologically intact children, clinically simulate malignant disease, and produce an acute nonspecific inflammatory lesion.     

Effects of amoxicillin treatment on the salivary microbiota in children with acute otitis media

Amoxicillin is a first-line antibiotic treatment for acute otitis media in children and one of the most commonly used antibiotics for human bacterial infections. We investigated changes in salivary bacterial communities among children treated with amoxicillin for acute otitis media (n = 18), using a culture-independent approach based on pyrosequencing of the V3 region of the bacterial 16S rRNA gene. The control group consisted of children with acute otitis media who were not given antibiotics (n = 15). One species-level phylotype assigned to the genus Streptococcus was identified across all (n = 99) saliva samples. Two additional species-level phylotypes from the genera Gemella and Granulicatella were shared by all (n = 45) samples of control subjects. Amoxicillin treatment resulted in reduced species richness and diversity, and a significant shift in the relative abundance of 35 taxa at different ranks from phylum to species-level phylotype. At the phylum level, prevalence of TM7 and Actinobacteria decreased at the end of treatment, whereas Proteobacteria had a higher relative abundance post-treatment. Multivariate analysis showed that samples from the same control subject taken over time intervals tended to cluster together. Among antibiotic-treated subjects, samples taken before and at the end of amoxicillin treatment formed two relatively well-separated clusters both of which greatly overlapped with samples taken about 3 weeks post-treatment. Our results point to a substantial but incomplete recovery of the salivary bacterial community from the antibiotic about 3 weeks after the end of treatment.     

Monitoring respiration in wheezy preschool children by pulse oximetry plethysmogram analysis

The aim of this study was to investigate whether respiratory information can be derived from pulse oximetry plethysmogram (pleth) recordings in acutely wheezy preschool children. A digital pulse oximeter was connected via ‘Bluetooth’ to a notebook computer in order to acquire pleth data. Low pass filtering and frequency analysis were used to derive respiratory rate from the pleth trace; the ratio of heart rate to respiratory rate (HR/RR) was also calculated. Recordings were obtained during acute wheezy episodes in 18 children of median age 31 months and follow-up recordings from 16 of the children were obtained when they were wheeze-free. For the acutely wheezy children, frequency analysis of the pleth waveform was within 10 breaths/min of clinical assessment in 25 of 29 recordings in 15 children. For the follow-up measurements, frequency analysis of the pleth waveform showed similarly good agreement in recordings on 15 of the 16 children. Respiratory rate was higher (p < 0.001), and HR/RR ratio was lower (p = 0.03) during acute wheeze than at follow-up. This study suggests that respiratory rate can be derived from pleth traces in wheezy preschool children.     

Patterns of Cytokines and Soluble Cellular Receptors in the Sera of Children with Acute Chagas' Disease

Cytokines and soluble cellular receptors are involved in inflammatory processes and probably in the pathogenesis of parasite and bacterial diseases. In a previous study, we reported increased levels of soluble receptors of interleukin-2 (sIL2-R) in children with acute Chagas' disease, one of the main parasitic infections that is endemic in Latin America. We sought to analyze the pattern of different cytokines and soluble receptors in the sera of children with chagasic infection. Children with acute and indeterminate stages of Chagas' disease, as well as nonchagasic children, were studied. Sera were assayed by enzyme-linked immunosorbent assay to measure the levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-2, IL-8, IL-12, sIL-2R, and the soluble receptors of CD8 and CD4 (sCD8 and sCD4). sIL-2R and sCD8 showed the highest levels in serum in acutely infected children, decreasing after specific antiparasite therapy. Chronic children showed a pattern similar to the one of nonchagasic children. Although they were not statistically significant, TNF-α, IL-6, and sCD4 showed a tendency to reach high levels in the acutely infected group, whereas IL-2, IL-8, and IL-12 did not reveal changes with respect to the noninfected children. In summary, we report here the patterns of cytokines and soluble receptors in in the sera of children infected with Trypanosoma cruzi; we found significantly increased levels of sIL-2R and sCD8 in acute infection that decreased after therapy, and high levels of TNF-α, IL-6, and sCD4 in some of the acute patients. The measurement of sIL-2R and sCD8 may provide a useful tool in the follow-up of children with Chagas' disease.     

Six cases of acute appendicitis with secondary peritonitis caused byStreptococcus pneumoniae

In six previously healthy children and adults with typical acute appendicitis,Streptococcus pneumoniae was isolated from peritoneal swabs or periappendicular pus in pure culture (four patients) or together with intestinal flora. Pneumococci recovered by abdominal paracentesis are not pathognomonic of socalled primary or spontaneous peritonitis.     

Bone Marrow versus Peripheral Blood from Unrelated Donors for Children and Adolescents with Acute Leukemia

Graft-versus-host disease (GVHD) rates are higher after unrelated donor transplantation; thus, we examined whether there would be differences in transplant outcomes by graft type in children and adolescents with acute leukemia. The primary endpoint was overall survival. We studied 872 patients <18 years old who were transplanted with bone marrow (n?=?650) or peripheral blood (n?=?222) from unrelated donors. The characteristics of the 2 groups were comparable, except recipients of bone marrow were younger than recipients of peripheral blood (median age, 10 versus 12 years). Grades 2 to 4 (hazard ratio [HR], 1.48; P < .001) and grades 3 and 4 acute (HR, 1.69; P < .001) and chronic GVHD (HR, 1.92; P < .001) were higher with transplantation of peripheral blood than with bone marrow. Although relapse risks were lower after peripheral blood transplants (HR, 0.76; P = .05), transplant-related mortality (HR, 1.91; P = .003) and overall mortality (HR, 1.34; P = .032) were higher than with bone marrow transplants. The 8-year probability of overall survival after transplantation of bone marrow was 47% compared with 42% after peripheral blood. The 8-year probability of leukemia-free survival was 40% after transplantation of bone marrow and peripheral blood. Lower relapse after transplantation of peripheral blood negated the survival advantage after transplantation of bone marrow. The observed higher acute and chronic GVHD seen with peripheral blood suggest cautious use of this graft in children and adolescents with acute leukemia.     

Acute bronchiolitis in a paediatric emergency department of Northern Greece. Comparisons between two decades

Introduction

Acute bronchiolitis is the most common lower respiratory tract infection in infants and toddlers concerning small bronchi or bronchioli. This retrospective study aimed to evaluate the incidence of acute bronchiolitis and the use of β₂-agonists between two different decades.

Material and methods

During 1990-1991 and 2001-2002, the files of the 2^nd Paediatric Emergency Department of Aristotle University of Thessaloniki, AHEPA Hospital were reviewed and cases of acute bronchiolitis were recorded and analysed.

Results

During 1990-1991, 14 538 children were identified with respiratory infections and bronchiolitis was diagnosed in 519/14 538 children (3.56%). Only 34 out of 519 patients received nebulised salbutamol (6.6%) and 221/519 were hospitalized (42.6%). During 2001-2002, 9001 children were found to have respiratory tract infections and acute bronchiolitis was diagnosed in 641/9001 of them (7.12%). In total, 411/641 children (64.1%) received salbutamol and ipratropium, and 89/641 patients (13.88%) were hospitalized. There was a predominance of male sex in both decades (p = 0.509). There was a statistically significant difference (p < 0.001) concerning the use of nebulised salbutamol with nebulised ipratropium between the two decades. Finally, during 2001-2002, the use of bronchodilators with or without corticosteroids was more frequent and it appears to be correlated with the reduced number of admissions to hospital (p < 0.05) compared with 1990-1991.

Conclusions

There was an increase in the incidence of acute bronchiolitis during the last decade. The admission rate decreased probably due to the use of nebulized salbutamol and ipratropium, but further multicentre comparative trials are required to define the role of bronchodilators in the treatment of acute bronchiolitis.     

Low incidence of human coronavirus among hospitalized children in Novosibirsk city,Russia during pre-pandemic period (2013–2020)

We investigated the incidence of 15 respiratory viruses among 2991 children with acute respiratory infections in Novosibirsk city, Russia, prior to the COVID-19 pandemic (2013–2020). Viral infections were detected in 72.5% cases. The incidence of human coronavirus was 2% (Alphacoronaviruses, 63%; Betacoronaviruses, 37%).     

Mycoplasma pneumoniae in children with acute and refractory asthma

BackgroundThe presence of Mycoplasma pneumoniae has been associated with worsening asthma in children. Sensitive assays have been developed to detect M pneumoniae–derived community-acquired respiratory distress syndrome (CARDS) toxin.ObjectivesTo identify the frequency and persistence of M pneumoniae detection in respiratory secretions of children with and without asthma and to evaluate antibody responses to M pneumoniae and the impact of M pneumoniae on biological markers, asthma control, and quality of life.MethodsWe enrolled 143 pediatric patients (53 patients with acute asthma, 26 patients with refractory asthma, and 64 healthy controls; age range, 5-17 years) during a 20-month period with 2 to 5 follow-up visits. We detected M pneumoniae using CARDS toxin antigen capture and polymerase chain reaction and P1 adhesin polymerase chain reaction. Immune responses to M pneumoniae were determined by IgG and IgM levels directed against CARDS toxin and P1 adhesin. pH was measured in exhaled breath condensates, and asthma control and quality of life were assessed using the Asthma Control Test and Pediatric Asthma Quality of Life Questionnaire.ResultsM pneumoniae was detected in 64% of patients with acute asthma, 65% with refractory asthma, and 56% of healthy controls. Children with asthma had lower antibody levels to M pneumoniae compared with healthy controls. Exhaled breath condensate pHs and asthma control and quality of life scores were lower in M pneumoniae–positive patients with asthma.ConclusionThe results suggest that M pneumoniae detection is common in children, M pneumoniae detection is associated with worsening asthma, and children with asthma may have poor humoral immune responses to M pneumoniae.