RESUMO
There were several factors associated with respiratory syncytial virus (RSV) severe acute lower respiratory infection (RSV-sALRI) in infants and young children. It is vital to develop a convenient scoring system to predict RSV-sALRI in children. Pediatric patients with RSV-ALRI from January 2009 to December 2021 were recruited retrospectively. Two-third of them were randomly grouped into the development set and one-third to the validation set. In the development set, risk factors for RSV-sALRI were transferred into the logistic regression analysis, then their receiver operating characteristic (ROC) curves were built to obtain the area under the ROC curve (AUC), and regression coefficients for each predictor were converted to points. Finally, the value of the scoring system was evaluated in the validation set. A total of 1 066 children with RSV-ALRI were recruited, including 710 in the development set and 356 in the validation set. By logistic regression analysis, six factors (younger than 2 years, gestational age <37 weeks, have siblings, birth weight ≤2500 g, artificial/mix feeding, CHD) showed statistical difference and then were scored with points according to the coefficient value (OR) in the development set. In the validation set, the sensitivity of the scoring system was 70.25%, the specificity 85.53%, the positive predictive value 71.43%, the negative predictive value 84.81%, and coincidence rate 0.80. The Kolmogorov-Smirnov test showed the distribution of AUC 0.765 (SE = 0.027; 95% CI = 0.713-0.818; p < 0.001). A simplified scoring system was developed in the study with high prediction value for RSV-sALRI in children.
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Recombination events in human adenovirus (HAdV) have led to some new highly pathogenic or infectious types. It is vital to monitor recombinant HAdVs, especially in children with acute respiratory tract infections (ARIs). In the retrospective study, HAdV positive specimens were collected from pediatric patients with ARIs during 2015 to 2021, then typed by sequence analysis of the penton base, hexon and fiber gene sequence. For those with inconsistent typing results, a modified method with species-specific primer sets of a fiber gene sequence was developed to distinguish co-infections of different types from recombinant HAdV infections. Then, plaque assays combined with meta-genomic next-generation sequencing (mNGS) were used to reveal the HAdV genomic characteristics. There were 466 cases positive for HAdV DNA (2.89%, 466/16,097) and 350 (75.11%, 350/466) successfully typed with the most prevalent types HAdV-B3 (56.57%, 198/350) and HAdV-B7 (32.00%, 112/350), followed by HAdV-C1 (6.00%, 21/350). Among 35 cases (7.51%, 35/466) with inconsistent typing results, nine cases were confirmed as co-infections by different types of HAdVs, and 26 cases as recombinant HAdVs in six genetic patterns primarily clustered to species C (25 cases) in pattern 1-5, or species D (1 case) in pattern 6. The novel recombinant HAdV of species D was identified with multiple recombinant events among HAdV-D53, HAdV-D64, and HAdV-D8, and officially named as HAdV-D115. High-frequency recombination of HAdVs in six genetic recombination patterns were identified among children with ARIs in Beijing. Specifically, there is a novel Adenovirus D human/CHN/S8130/2023/115[P22H8F8] designed as HAdV D115.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Filogenia , Recombinação Genética , Infecções Respiratórias , Humanos , Adenovírus Humanos/genética , Adenovírus Humanos/classificação , Adenovírus Humanos/isolamento & purificação , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Infecções por Adenovirus Humanos/virologia , Infecções por Adenovirus Humanos/epidemiologia , Pré-Escolar , Estudos Retrospectivos , Masculino , Criança , Lactente , Feminino , Pequim/epidemiologia , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Coinfecção/virologia , Coinfecção/epidemiologia , DNA Viral/genética , Genoma Viral/genética , Adolescente , China/epidemiologiaRESUMO
BACKGROUND: Previous serological studies of human bocavirus (HBoV) 1 could not exclude cross-reactivity with the other three HBoVs, particularly HBoV2. METHODS: To search for genotype-specific antibodies against HBoV1 and HBoV2, the divergent regions (DRs) located on the major capsid protein VP3 were defined through viral amino acid alignment and structure prediction. DR-deduced peptides were used as antigens to harvest corresponding anti-DR rabbit sera. To determine their genotype specificities for HBoV1 and HBoV2, these sera samples were used as antibodies against the antigens VP3 of HBoV1 and HBoV2 (expressed in Escherichia coli) in western blotting (WB), enzyme-linked immunosorbent assay (ELISA), and bio-layer interferometry (BLI) assays. Subsequently, the antibodies were evaluated with clinical specimens from pediatric patients with acute respiratory tract infection by indirect immunofluorescence assay (IFA). RESULTS: There were four DRs (DR1-4) located on VP3 with different secondary and tertiary structures between HBoV1 and HBoV2. Regarding the reactivity with VP3 of HBoV1 or HBoV2 in WB and ELISA, high intra-genotype cross-reactivity of anti-HBoV1 or HBoV2 DR1, DR3, and DR4, but not anti-DR2, was observed. Genotype-specific binding capacity of anti-DR2 sera was confirmed by BLI and IFA, in which only anti-HBoV1 DR2 antibody reacted with HBoV1-positive respiratory specimens. CONCLUSION: Antibodies against DR2, located on VP3 of HBoV1 or HBoV2, were genotype specific for HBoV1 and HBoV2, respectively.
Assuntos
Bocavirus Humano , Infecções por Parvoviridae , Infecções Respiratórias , Animais , Criança , Humanos , Coelhos , Bocavirus Humano/genética , Infecções por Parvoviridae/diagnóstico , Ensaio de Imunoadsorção Enzimática , Genótipo , Infecções Respiratórias/diagnóstico , Escherichia coliRESUMO
Background: Human bocavirus 1 (HBoV1), first discovered in 2005, was positive in symptomatic and healthy children and co-detected with other respiratory viruses. It is a long journey to decisively demonstrate the unique viral pathogenic function of acute respiratory tract infection (ARTI) in pediatric patients. Methods: Respiratory specimens collected from pediatric patients with ARTI from January 2017 to December 2021 were screened by a capillary electrophoresis-based multiplex PCR (CEMP) assay, then genotyped by PCR and sequencing for HBoV1. For the antigen test, a part of HBoV1 DNA positive nasopharyngeal aspirates (NPAs) was used as an antigen, while a rabbit anti-HBoV1 DR2 specific to HBoV1 was used as an antibody in the indirect-immunofluorescence assay (IFA). Finally, the levels of IgG specific to HBoV1 in acute and convalescent sera selected retrospectively from only HBoV1 DNA-positive patients were evaluated by IFA. Results: Among 9,899 specimens, 681 were positive for HBoV1 DNA (6.88%, 681/9899), which included 336 positives only for HBoV1 (49.34%, 336/681) and 345 (50.66%, 345/681) positives also for other pathogens. In the antigen test, there were 37 among 47 NPAs determined as HBoV1 antigen-positive (78.72%, 37/47), including 18 (48.65%, 18/37) positives solely for HBoV1 DNA. Among 4 pediatric patients with both acute and convalescent sera, there was one positive for HBoV1 antigen (D8873) and 2 lack the antigen results (D1474 and D10792), which showed seroconversion with a ≥ 4-fold increase in IgG levels. Conclusions: The combination results of nucleic acid, antigen, and serology tests answered that HBoV1 is a genuine pathogen for ARTI in pediatric patients.
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Purpose: Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients. Methods: The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated. Results: The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1ß in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1ß in the first serum samples from patients with ON1 compared to those with BA9 of subtype B. Conclusions: Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.
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Evasão da Resposta Imune , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Humanos , Genótipo , Interleucina-1alfa , Palivizumab/farmacologia , Filogenia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/genéticaRESUMO
Restless legs syndrome (RLS), with a lifetime prevalence of up to 10%, is a frequent neurological disease and the most common movement disorder in sleep. A compulsive urge to move the legs with sensory symptoms and sleep disturbances can significantly impair the quality of life. Furthermore, RLS frequently occurs as a comorbidity to various internal and neurological diseases. It is diagnosed clinically based on the five essential diagnostic criteria. For treatment, an iron deficiency should first be excluded. Drugs approved for the treatment of RLS include dopaminergics (L-DOPA/benserazide) and dopamine agonists as well as oxycodone/naloxone, as a second-line treatment in severe cases. Augmentation as a deterioration of symptoms is a clinically defined complication of high-dose dopaminergic treatment, requiring special management strategies. Due to its high prevalence of up to 25%, RLS plays also an important role in the care of pregnant women.
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Síndrome das Pernas Inquietas , Transtornos do Sono-Vigília , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Gravidez , Qualidade de Vida , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/epidemiologia , SonoRESUMO
We evaluated two currently available rapid antigen detection tests (RADTs) for Respiratory syncytial virus (RSV), Sofia® RSV FIA and BinaxNOW RSV Card (BinaxNOW). Between November 2017 and February 2018, 395 nasopharyngeal swabs were collected from children diagnosed with acute respiratory infections. The swabs were evaluated using the aforementioned RADTs, the reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR), and the direct immunofluorescence assay (DFA). The sensitivity of Sofia® RSV FIA (80.82%) was significantly higher than that of BinaxNOW (53.42%) when RT-qPCR was used as the standard. This was confirmed with DFA. The sensitivities of Sofia® RSV FIA (85.4% [41/48]) and BinaxNOW (58.3% [28/48]) were higher for RSV A than for RSV B (69.6% [16/23] and 43.5% [10/23], respectively). The optimal critical cycle threshold (Ct) values on RT-qPCR that correlated with Sofia® RSV FIA and BinaxNOW were 24 and 22, respectively. The kappa value for Sofia® RSV FIA and RT-qPCR was 0.962 in patients who were two years old or younger, but 0.648 in those who were more than two years old. Thus, Sofia® RSV FIA is more sensitive than BinaxNOW; its results were affected by the RSV viral strain and load. Sofia® RSV FIA is more effective in children who are ≤ 2 years old than in those who are > 2 years old.
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Antígenos Virais/isolamento & purificação , Técnica Direta de Fluorescência para Anticorpo/normas , Kit de Reagentes para Diagnóstico/normas , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/isolamento & purificação , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Nasofaringe/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Human bocaviruses (HBoVs), which were first identified in 2005 and are composed of genotypes 1-4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. To investigate if HBoV infection is a risk factor of acute gastroenteritis in children younger than 5 years old, we searched PubMed, Embase (via Ovid), the Chinese Biomedical Literature Database (CBM), and the Cochrane Library for studies assessing the prevalence of HBoVs in individuals from Oct 25, 2005 to Oct 31, 2016. We included studies using PCR-based diagnostics for HBoVs from stool specimens of patients with or without acute gastroenteritis that carried out research for over 1 year on pediatric patients aged younger than 5 years old. The primary outcome was the HBoV prevalence among all cases with acute gastroenteritis. Pooled estimates of the HBoV prevalence were then generated by fitting linear mixed effect meta-regression models. Of the 36 studies included, the pooled HBoV prevalence in 20,591 patients with acute gastroenteritis was 6.90% (95% confidence interval (95% CI): 5.80-8.10%). In the ten studies with a control group, HBoVs were detected in 12.40% of the 3,620 cases with acute gastroenteritis and in 12.22% of the 2,030 control children (odds ratio (OR): 1.44; 95% CI: 0.95-2.19, p = 0.09 between case and control groups). HBoV1 and HBoV2 were detected in 3.49% and 8.59% of acute gastroenteritis cases, respectively, and in 2.22% and 5.09% of control children, respectively (OR: 1.40; 95% CI: 0.61-3.25; p = 0.43 and OR: 1.68; 95% CI: 1.21-2.32; p = 0.002, respectively). Current evidence suggests that the overall HBoV prevalence in children younger than 5 years old is not significantly different between groups with or without acute gastroenteritis. However, when HBoV1 was excluded, the HBoV2 prevalence was significantly different between these two groups, which may imply that HBoV2 is a risk factor of acute gastroenteritis in children younger than 5 years old.
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Gastroenterite/virologia , Bocavirus Humano/genética , Infecções por Parvoviridae/epidemiologia , Pré-Escolar , Feminino , Genótipo , Bocavirus Humano/classificação , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Parvoviridae/complicações , PrevalênciaRESUMO
Cardiac L-type calcium channel (CaV1.2), calmodulin (CaM), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) form the CaV1.2/CaM/CaMKII signaling pathway, which plays an important role in maintaining intracellular Ca(2+) homeostasis. The roles of CaM and CaMKII in the regulation of CaV1.2 in Ca(2+)-dependent inactivation and facilitation have been reported; however, alterations in this signaling pathway in the heart after myocardial ischemia (MI) had not been well characterized. In this study, we investigated the dynamic changes in CaV1.2, CaM, and CaMKII mRNA and protein expression levels in the left ventricles of the heart following MI in rats. The MI model was induced by ligating the left anterior descending coronary artery; the rats were divided into the following five groups: the 6 h post-MI group (MI-6h), 24 h post-MI group (MI-24h), 1 week post-MI group (MI-1w), 2 weeks post-MI group (MI-2w), and the sham group. The mRNA levels were measured by quantitative real-time polymerase chain reaction and the protein expression was determined by western blotting and immunohistochemistry. There were no observable differences in the CaV1.2 mRNA and protein levels at the early stages of MI, but these levels decreased at MI-2w. Both the mRNA and protein levels of CaM increased at MI-6h, peaked at MI-24h, and then reduced to normal levels at MI-2w. CaMKII mRNA and protein levels decreased at MI-6h and reached their lowest level at MI-24h. Taken together, these data demonstrate that there are dynamic changes in the CaV1.2/CaM/CaMKII signaling pathway following MI injuries, which suggests that different therapeutic regimens should be used at different time points after MI injuries.