Case report: Influenza A virus and Human herpesvirus 1 infection-associated acute encephalopathy in children with the mutations in the SLC25A19 andTICAM1 gene, respectively.

Background: Infection-associated acute encephalopathy (AE) is a clinical condition caused by a variety of pathogens, particularly common viruses. In some cases, this condition could be characterized by a sudden onset and a rapid progression, leading to severe neurological sequelae, including acute encephalopathy with biphasic seizures and late reduced diffusion, hemorrhagic shock and encephalopathy syndrome, etc. Case presentation: In this study, it was reported that three previously healthy children developed acute encephalopathy/encephalitis symptoms with different neurological sequelae after either Influenza A Virus or Human Herpesvirus 1 infection, presenting with fever and convulsions. What's more, after performing the gene exon detection for these three children, it was found that there are abnormal genes corresponding to their neurological sequelae, including SLC25A19 and TICAM1. Conclusions: Therefore, comparing to children with common encephalitis, for children with encephalitis whose progression is rapid and clinical manifestations such as recurrent fever and frequent convulsions is difficult to improve, whole-exome sequencing can be a valuable tool for identifying encephalitis-associated genetic variants and providing strong evidence for prognostic prediction.

Pathogens in PICU before and during the SARS-CoV-2 pandemic in China: a multicenter retrospective study.

BACKGROUND: Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. METHODS: This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. RESULTS: In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). CONCLUSION: After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.

Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.

BACKGROUND: Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis. RESULTS: We report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic. CONCLUSIONS: Exome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.

Continuous Blood purification on Influenza-Associated Neurological Disease in children: a retrospective cohort study.

BACKGROUND: Due to lack of proven therapies, we evaluated the effect of CBP on Influenza-Associated Neurological Disease in children. METHODS: A single-center, retrospective, cohort study was conducted in Luoyang, Henan province, China from January 2018 to January 2020. Children (<18 years) with influenza-associated neurological disease were enrolled in the study. Children with indications for CBP and parental consent received CBP (Continuous Blood purification), while others received maximal intensive care treatment because of the absence of parental consent. The outcomes of the CBP and non-CBP groups were compared. Categorical variables were presented as percentage and compared by Chi-square test. Continuous variables were expressed as median (interquartile ranges) and compared with non-parametric independent sample test. Statistical analyses were carried out by SPSS (version 26.0) and p < 0.05 (2 tailed) was considered to be statistically significant. RESULTS: 30 children with influenza-associated neurological disease were recruited to the study. 18 received CBP and the other 12 received maximal intensive care. There were no differences between CBP and non-CBP children in age, sex, body weight, type of influenza virus, neurological complications, Glasgow score, PIM-2 score and PCIS at admission (p > 0.05). The inflammatory factors (CRP, PCT and IL-6) of 30 cases were tested at admission and after 3 days of admission. In the CBP group, there was a significant decrease in IL-6 levels at 3 days of admission (p = 0.003) and a decrease in CRP and PCT levels, but no significant difference (p > 0.05). In the non-CBP group, there were no significant difference on levels of CRP, PCT and IL-6 at admission and 3-day of admission (p > 0.05). The 28-day mortality was significantly lower in the CBP group compared with the non-CBP group (11.11% vs. 50%, p = 0.034). CONCLUSIONS: CBP definitely reduces IL-6 levels significantly. We did find that the survival rate of patients in the CBP group was improved. But we don't know if there is a relationship between the reduction of IL-6 levels and the survival rate. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (ChiCTR2000031754).

[Correlation between Mycoplasma pneumoniae DNA replication level and disease severity in children with severe Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the correlation of Mycoplasma pneumoniae DNA (MP-DNA) replication level in throat swab and bronchoalveolar lavage fluid (BALF) with disease severity in children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A total of 44 children with SMPP who underwent bronchoalveolar lavage were enrolled as subjects. The serum levels of cytokines and MP-DNA replication times in throat swab were measured in the acute stage and the recovery stage, and the levels of interleukin (IL)-8 and MP-DNA replication times in BALF were measured in the acute stage. According to whether mechanical ventilation was needed for respiratory failure, the children were divided into a mechanical ventilation group (n=19) and a non-mechanical ventilation group (n=25), and the two groups were compared in MP-DNA replication times in BALF. RESULTS: For the children with SMPP, serum levels of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, IL-1, IL-6, IL-8, and IL-18 in the acute stage were significantly higher than those in the recovery stage (P<0.05). In the acute stage, MP-DNA replication times in throat swab were positively correlated with those in BALF (r=0.613, P<0.05), and MP-DNA replication times in BALF were positively correlated with IL-18 levels in peripheral blood and BALF (r=0.613 and 0.41 respectively, P<0.05). Compared with the non-mechanical ventilation group, the mechanical ventilation group had significantly higher MP-DNA replication times in BALF, a significantly longer duration of systemic hormone treatment, significantly higher serum levels of lactate dehydrogenase and IL-18, and significantly higher white blood cell count and IL-18 level in BALF (P<0.05). CONCLUSIONS: In children with SMPP, MP-DNA replication level in throat swab and BALF can be used as a reference index for the assessment of disease severity.