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To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.
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Infecciones por Enterovirus , Infecciones por Picornaviridae , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Preescolar , Anciano , Rhinovirus/genética , Prevalencia , Infecciones por Picornaviridae/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , China/epidemiología , Variación GenéticaRESUMEN
A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis-based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV-A replaced RSV-B in July 2021 to become the dominant subtype. Six RSV-A and eight RSV-B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.
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COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/prevención & control , Beijing/epidemiología , Filogenia , COVID-19/epidemiología , COVID-19/prevención & control , Virus Sincitial Respiratorio Humano/genética , Reacción en Cadena de la Polimerasa MultiplexRESUMEN
BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , COVID-19 , Infecciones del Sistema Respiratorio , Niño , Humanos , Beijing/epidemiología , Adenovirus Humanos/genética , Filogenia , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , China/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Reacción en Cadena de la Polimerasa MultiplexRESUMEN
BACKGROUND: The coronavirus disease 2019 outbreak has hit Beijing since mid-Nov, 2022, with soaring growth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. Therefore, it is vital to determine the clinical manifestations of epidemic SARS-CoV-2 strains in paediatric patients. METHODS: In this study, nucleic acid tests (NATs) for SARS-CoV-2 were performed in paediatric outpatients with symptoms of acute respiratory tract infection during 18 Nov-6 Dec, 2022. Half of the outpatients positive for SARS-CoV-2 were randomly selected to screen for other respiratory pathogens, whereas those with low cycle threshold values in SARS-CoV-2 NATs were amplified and sequenced to determine the SARS-CoV-2 variants. Finally, children positive for SARS-CoV-2 with clinical information in detail were enrolled in a follow-up study to identify potential factors significantly associated with long recovery. RESULTS: Among 9625 paediatric outpatients tested for nucleic acid of SARS-CoV-2, 733 (7.62%, 733/9625) were identified as SARS-CoV-2 NAT positive, with only three (0.82%, 3/366) co-infected with other pathogens among 366 randomly selected patients, and 71 (62.83%) determined as Omicron subvariant BF.7 and 42 (37.22%) as BA.5.2 among 113 successfully sequenced. Among the 681 patients with complete clinical information, fever was the most common symptom (96.8%). In a follow-up study of 592 patients, 46.96% became asymptomatic on the third day and 65.71% on the fifth day. Only 1.7% of infected children experienced febrile seizures. Combined with abnormal C-reactive protein, a higher percentage of antibiotics administration was observed. More co-living members and longer duration of first symptoms served as independent risk factors for long-term recovery, especially in children vaccinated for SARS-CoV-2. CONCLUSIONS: BF.7 and BA.5.2 were the dominate Omicron subvariants and caused milder infections during the SARS-CoV-2 outbreak in Beijing. The number of co-living members and duration of first symptoms were independent risk factors for long-term recovery.
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COVID-19 , Ácidos Nucleicos , Humanos , Niño , Beijing/epidemiología , Estudios de Seguimiento , SARS-CoV-2/genética , COVID-19/epidemiologíaRESUMEN
Infections caused by bovine herpesvirus 1 (BoHV-1) remain a serious global issue to the health and welfare of the bovine industry. Monitoring of neutralizing antibodies is essential not only for epidemic diagnosis, but also to assess vaccination efficacy. In this study, we generated a neutralizing monoclonal antibody, termed as 3F8, targeting glycoprotein D (gD) of BoHV-1. This monoclonal antibody could neutralize BoHV-1 with a 50% inhibitory concentration (IC50) of 37.82 ng/mL. Furthermore, 3F8 could inhibit BoHV-1 infection and cell-to-cell spread at the prebinding stage. A blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies against BoHV-1 was then developed based on 3F8 and protein gD generated using a baculovirus expression system. The sensitivity and specificity of the test were estimated to be 94.59% and 93.42%, respectively. A significant correlation (R2 = 0.9583, p < 0.01) was observed between the results obtained with the blocking ELISA and a virus neutralization test, which suggested that the blocking ELISA could detect neutralizing antibodies against BoHV-1. A serological survey was carried out in the dairy farms in Beijing district using 3F8-based blocking ELISA to monitor the annual neutralization antibody against BoHV-1 during 2012-2020. It revealed that the dairy farms in Beijing were at high risk of BoHV-1 infection during 2012-2017 but were protected since 2018 upon implementation of an immunization program. Our results demonstrated that this assay is suitable for BoHV-1 surveillance and vaccination efficacy in cattle as a replacement for the virus neutralization test. KEY POINTS: ⢠Prevention of BoHV-1 infection requires the monitoring of neutralizing antibodies. ⢠A blocking ELISA for the neutralizing antibody was developed based on mAb 3F8 against BoHV-1 gD. ⢠It can replace the labor-intensive and time-consuming viral neutralizing tests.
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Infecciones por Herpesviridae , Herpesvirus Bovino 1 , Animales , Bovinos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática/métodos , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Anticuerpos Monoclonales , VacunaciónRESUMEN
A comparative analysis of confirmed cases of human influenza virus (HIFV), human respiratory syncytial virus (HRSV), and human metapneumovirus (HMPV) was conducted to describe their clinical and epidemiological characteristics. During 2009-2021, active surveillance of acute respiratory infections (ARIs) was performed in nine provinces of China. Clinical and epidemiological information and laboratory testing results of HIFV, HRSV, and HMPV were analyzed. Among 11591 ARI patients, the single-infection rates of HIFV, HRSV, and HMPV were 15.00%, 9.59%, and 2.24%, respectively; the coinfection rate of these three viruses was 0.64%. HIFV infection was mainly in adults aged 15-59 years, accounting for 39.10%. HRSV and HMPV infections were mainly in children under 5 years old, accounting for 87.13% and 83.46%, respectively. Patients with HRSV infection were younger than HMPV. HRSV and HMPV had high similarities in clinical manifestations, presenting with lower respiratory symptoms. HIFV mainly presented with an upper respiratory infection. The epidemic peak of HRSV was earlier than that of HIFV, and that of HMPV was later than those of HRSV and HFIV. A total of 85.14% of coinfection cases were children under 5 years old. Coinfection might increase the risk of pneumonia in HIFV cases. During 2020-2021, the positive rates and seasonal patterns of these three viruses changed due to the impact of the COVID-19 pandemic. Certain clinical and epidemiological features were observed in HIFV, HRSV, and HMPV infections, which could be beneficial for guiding clinical diagnosis, treatment, and prevention of these three viruses in China.
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COVID-19 , Coinfección , Gripe Humana , Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Adulto , Niño , Preescolar , China/epidemiología , Coinfección/epidemiología , Humanos , Lactante , Gripe Humana/epidemiología , Pandemias , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
BACKGROUND: The aim of the present study was to develop a clinical scoring system for the diagnosis of hand-foot-mouth disease (HFMD) with improved accuracy. METHODS: A retrospective analysis was performed on standardized patient history and clinical examination data obtained from 1435 pediatric patients under the age of three years who presented with acute rash illness and underwent enterovirus nucleic acid detection. Patients were then divided into the HFMD (1094 patients) group or non-HFMD (341 patients) group based on a positive or a negative result from the assay, respectively. We then divided the data into a training set (1004 cases, 70%) and a test set (431 cases, 30%) using a random number method. Multivariate logistic regression was performed on 15 clinical variables (e.g. age, exposure history, number of rash spots in a single body region) to identify variables highly predictive of a positive diagnosis in the training set. Using the variables with high impact on the diagnostic accuracy, we generated a scoring system for predicting HFMD and subsequently evaluated this system in the test set by receiver operating characteristic curve (ROC curve). RESULTS: Using the logistic model, we identified seven clinical variables (age, exposure history, and rash density at specific regions of the body) to be included into the scoring system. The final scores ranged from - 5 to 24 (higher scores positively predicted HFMD diagnosis). Through our training set, a cutoff score of 7 resulted in a sensitivity of 0.76 and specificity of 0.68. The area under the receiver operating characteristic curve (AUC) was 0.804 (95% confidence interval [CI]: 0.773-0.835) (P < 0.001). Using the test set, we obtained an AUC of 0.76 (95% CI: 0.710-0.810) with a sensitivity of 0.76 and a specificity of 0.62. These results from the test set were consistent with those from the training set. CONCLUSIONS: This study establishes an objective scoring system for the diagnosis of typical and atypical HFMD using measures accessible through routine clinical encounters. Due to the accuracy and sensitivity achieved by this scoring system, it can be employed as a rapid, low-cost method for establishing diagnoses in children with acute rash illness.
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Infecciones por Enterovirus , Enterovirus , Enfermedad de Boca, Mano y Pie , Niño , Preescolar , Enfermedad de Boca, Mano y Pie/diagnóstico , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Lactante , Curva ROC , Estudios RetrospectivosRESUMEN
Coxsackievirus A16 (CVA16) is a major pathogen that causes hand, foot, and mouth disease (HFMD). The recombination form (RF) shifts and global transmission dynamics of CVA16 remain unknown. In this retrospective study, global sequences of CVA16 were retrieved from the GenBank database and analyzed using comprehensive phylogenetic inference, RF surveys, and population structure. A total of 1,663 sequences were collected, forming a 442-sequences dataset for VP1 coding region analysis and a 345-sequences dataset for RF identification. Based on the VP1 coding region used for serotyping, three genotypes (A, B, and D), two subgenotypes of genotype B (B1 and B2), and three clusters of subgenotype B1 (B1a, B1b, and B1c) were identified. Cluster B1b has dominated the global epidemics, B2 disappeared in 2000, and D is an emerging genotype dating back to August 2002. Globally, four oscillation phases of CVA16 evolution, with a peak in 2013, and three migration pathways were identified. Europe, China, and Japan have served as the seeds for the global transmission of CVA16. Based on the 3D coding region of the RFs, five clusters of RFs (RF-A to -E) were identified. The shift in RFs from RF-B and RF-C to RF-D was accompanied by a change in genotype from B2 to B1a and B1c and then to B1b. In conclusion, the evolution and population dynamics of CVA16, especially the coevolution of 3D and VP1 genes, revealed that genotype evolution and RF replacement were synergistic rather than stochastic.
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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.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Filogenia , Recombinación Genética , Infecciones del Sistema Respiratorio , Humanos , Adenovirus Humanos/genética , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Adenovirus Humanos/virología , Infecciones por Adenovirus Humanos/epidemiología , Preescolar , Estudios Retrospectivos , Masculino , Niño , Lactante , Femenino , Beijing/epidemiología , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Coinfección/virología , Coinfección/epidemiología , ADN Viral/genética , Genoma Viral/genética , Adolescente , China/epidemiologíaRESUMEN
Human adenovirus serotype 31 (HAdV-31) is closely associated with gastroenteritis in children and can cause fatal systemic disseminated diseases in immunocompromised patients. The lack of genomic data for HAdV-31, especially in China, will greatly limit research on its prevention and control. Sequencing and bioinformatics analyses were performed for HAdV-31 strains from diarrheal children in Beijing, China, during 2010-2022. Three capsid protein genes (hexon, penton, and fiber) were obtained in 37 cases, including one in which the whole genome was sequenced. HAdV-31 strains clustered into three distinct clades (I-III) in a phylogenetic tree constructed based on concatenated genes and the whole genome; the endemic strains only gathered into clade II, and most of the reference strains clustered into clade I. Compared with penton and hexon, fiber had a faster evolutionary rate (1.32 × 10-4 substitutions/site/year), an earlier divergence time (1697), lower homology (98.32-100% at the amino acid level), and greater genetic variation (0.0032). Four out of the six predicted positive selection pressure codons were also in the knob of fiber. These results reveal the molecular evolution characteristics and variations of HAdV-31 in Beijing, and fiber may be one of the main evolution driving forces.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Niño , Humanos , Beijing/epidemiología , Adenovirus Humanos/genética , Filogenia , Serogrupo , China/epidemiología , Evolución Molecular , Análisis de Secuencia de ADN/métodos , Variación GenéticaRESUMEN
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.
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Bocavirus Humano , Infecciones por Parvoviridae , Infecciones del Sistema Respiratorio , Animales , Niño , Humanos , Conejos , Bocavirus Humano/genética , Infecciones por Parvoviridae/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Genotipo , Infecciones del Sistema Respiratorio/diagnóstico , Escherichia coliRESUMEN
OBJECTIVE: To explore the clinical features of types 3 and 7 adenovirus pneumonia in children and compare the difference between two types. METHODS: A total of 47 patients with adenovirus pneumonia at our hospital from January 2009 to June 2011 were reviewed. According to the serological types, they were divided into two groups: type 3 (n = 19) and type 7 (n = 28). Two groups were analyzed statistically with regards to age, gender, clinical presentation, critical scores, laboratory examinations, radiographic findings, lung function changes, complications and prognosis respectively. RESULTS: For types 3 and 7 adenovirus pneumonia, the median age of onset were 1.8 and 1.1 years old respectively. The male-to-female ratio were 14:5 and 20:8 respectively. As compared with type 3, type 7 had the longer fever time ((18 ± 10) vs (11 ± 7)days, P = 0.010), the higher critical proportion (13/28 (46.4%) vs 3/19 (15.8%), P = 0.031), the longer hospital stays ((28 ± 17) vs (15 ± 6) days, P = 0.003)), the higher proportion of involved lung ≥ 3 lobes (22/28 (78.6%) vs 4/19 (21.1%), P = 0.000), the lower oxygenation index ((192 ± 85) vs (256 ± 79) mm Hg,1 mm Hg = 0.133 kPa, P = 0.011), the higher proportion of mechanical ventilation (17/28 (60.7%) vs 5/19 (26.3%), P = 0.020) and the higher proportion of multiple organ dysfunction syndrome (16/28 (57.1%) vs 5/19 (26.3%), P = 0.037). In type 7, organ dysfunction was more obvious, particularly in nervous system, blood system and enzyme changes. Three cases of type 7 had pulmonary sequela with small airway disease. CONCLUSION: With more severe clinical manifestations, laboratory parameters and imaging data than type 3, type 7 adenovirus pneumonia in children is more likely to cause pulmonary sequela.
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Adenovirus Humanos/clasificación , Neumonía Viral/virología , Adenoviridae , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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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Evasión Inmune , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Humanos , Genotipo , Interleucina-1alfa , Palivizumab/farmacología , Filogenia , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/genéticaRESUMEN
BACKGROUND: Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are two major etiological agents of Hand, Foot and Mouth Disease (HFMD). EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to. RESULTS: The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C). VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (χ(2) = 5.02, P < 0.05) as well as EV71 VP4 and CA16 VP4 (χ(2) = 15.30, P < 0.01) in the detection of IgG against recombinant proteins with same batch of serum samples. The sera-positive rate of IgG against VP1 was higher than that against VP4 for both EV71 (χ(2) = 26.47, P < 0.01) and CA16 (χ(2) = 16.78, P < 0.01), which might be because of different positions of VP1 and VP4 in the capsid of the viruses. CONCLUSIONS: EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different.
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Proteínas de la Cápside/genética , Infecciones por Coxsackievirus/virología , Enterovirus Humano A/genética , Enterovirus/genética , Anticuerpos Antivirales/sangre , Niño , China/epidemiología , Infecciones por Coxsackievirus/epidemiología , Infecciones por Coxsackievirus/inmunología , ADN Viral/genética , Enterovirus/inmunología , Enterovirus Humano A/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Filogenia , Proteínas Recombinantes/genética , Análisis de Secuencia de ADNRESUMEN
Human adenovirus serotype 41 (HAdV-F41) is an important pathogen that causes diarrhea in children. However, the data on its molecular genetic characteristics and evolutionary history are still neither comprehensive nor sufficient. Four capsid protein genes from 58 HAdV-F41-positive specimens taken from diarrheal children in Beijing during 2010-2019 were amplified and analyzed. Variant amino acids in the hexon gene (18 sites) and short fiber gene (4 sites) clustered these strains into two clades and four subclades. The deletion of 15 amino acids found in the gene seemed to have little effect on the genomic strain cluster same as to penton gene. The HAdV-F41 strains had high diversity, as assessed from the intraspecific recombination of hexon, short fiber and long fiber. The molecular evolutionary rate of HAdV-F41's concatenated genes was 4.07 × 10-5 substitutions/site/year, and it diverged from the most recent common ancestor in 1720. Apart from in the penton gene, positive selection codons were predicted in the other three genes, which may play a synergistic role in the evolution of HAdV-F41. These results provide new insights for understanding the characteristics of infectivity and developing vectors and vaccine vehicles for HAdV-F41.
Asunto(s)
Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/genética , Proteínas de la Cápside/genética , Evolución Molecular , Variación Genética , Secuencia de Aminoácidos , Beijing , Proteínas de la Cápside/química , Proteínas de la Cápside/metabolismo , Humanos , Alineación de Secuencia , SerogrupoRESUMEN
BACKGROUND: Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. METHODS: Throat swabs were collected from children with HFMD and suspected HFMD during 2010-2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. RESULTS: A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010-2012 followed by an apparent decline during 2013-2017. However, the activities of CVA16 increased gradually during 2018-2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10-3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. CONCLUSIONS: The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010-2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.
Asunto(s)
Enterovirus , Enfermedad de Boca, Mano y Pie , Beijing/epidemiología , Niño , Preescolar , China/epidemiología , Enterovirus/genética , Enfermedad de Boca, Mano y Pie/diagnóstico , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Epidemiología Molecular , FilogeniaRESUMEN
BACKGROUND: A series of public health preventive measures has been widely implemented in Beijing to control the coronavirus disease-19 (COVID-19) pandemic since January 2020. An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary. METHODS: Respiratory specimens collected from children with acute respiratory infections were tested by NxTAG™ respiratory pathogen panel assays during January 2017 and December 2020. Specimens characterized as rhinoviruses (RVs) were sequenced to identify the RV species and types. Then, the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0. RESULTS: The positive rates of adenovirus (ADV), influenza virus (flu), RVs, and respiratory syncytial virus (RSV) dropped abruptly by 86.31%, 94.67%, 94.59%, and 92.17%, respectively, from February to May 2020, compared with the average level in the same period during 2017-2019. Positive rates of RVs then steeply increased from June 2020 (13.77%), to an apex (37.25%) in August 2020, significantly higher than the average rates (22.51%) in August 2017-2019 (P = 0.005). The increase, especially in group ≥ 3 years, was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing. CONCLUSIONS: Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures, the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.
Asunto(s)
COVID-19 , Infecciones del Sistema Respiratorio , Beijing/epidemiología , Niño , China/epidemiología , Hospitales , Humanos , Lactante , Pandemias , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Rhinovirus , SARS-CoV-2RESUMEN
Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95 (5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1 (8.6%), 30 HAdV-3 (37.0%), two HAdV-6 (2.5%), and 42 HAdV-7 (51.9%). More HAdV-positive samples were collected in August (4.7%, 12/255), September (15.0%, 41/274) and October (6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases (4.2%, 77/1840; 81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.