Early change of retinal nerve fiber layer in children with type 1 diabetes mellitus in northern China.

OBJECTIVES: This study aimed to identify discrepancies in the retinal nerve fiber layer (RNFL) between type 1 diabetes mellitus (T1DM) children without retinopathy and healthy subjects in northern China. METHODS: This was a cross-sectional hospital-based study carried out from Jan 2019 until Jul 2021 at the department of pediatrics in Tianjin medical university general hospital. Children with T1DM but no retinal disease were screened. RNFL thickness was obtained via spectral domain optical coherence tomography. Disease duration, HbA1c, 25-hydroxyvitamin D level, insulin regimen, and diet control status were also collected. RESULTS: A total of 20 children with T1DM and 20 matched health participants were enrolled. The mean age in the T1DM group was 10.3 ± 2.8 years, and the median duration of diabetes was 1 (range 1-3) year. Children with T1DM had thinner average RNFL than control subjects (105 ± 6 vs. 110 ± 11 µm, p=0.008), especially in temporal and nasal parts. There was a significant negative association between HbA1c levels and the RNFL thickness in the T1DM group (B (95 % confidence interval): -4.313 (-7.055 to -1.571); p=0.005). CONCLUSIONS: In our study, the decreased thickness of RNFL was negatively associated with elevated HbA1c in children with early stages of T1DM.

Molecular Epidemiology and Clinical Features of Enteroviruses-Associated Hand, Foot, and Mouth Disease and Herpangina Outbreak in Zunyi, China, 2019.

Background: Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases. Methods: We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types. Results: From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher. Conclusions: The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.

Panton-Valentine leukocidin gene sequence variation and phage in methicillin-resistant and methicillin-susceptible Staphylococcus aureus from children in mainland China.

To determine the variation in the Panton-Valentine leukocidin (PVL) gene sequences and different PVL-encoding phages of Staphylococcus aureus strains collected from children in mainland China, fifty-eight strains with PVL collected from 2007 to 2009 were used. Their molecular characteristics were examined. Primers were designed to sequence the PVL genes. Six PVL-encoding phages (ϕPVL, ϕ108PVL, ϕSLT, ϕSa2MW, ϕSa2958, and ϕSa2USA) were identified by PCR. Eleven sequence types (ST) were detected with ST59 (39.7%, 23/58) the most frequent ST, followed by 910 (22.4%, 13/58), and 338 (12.1%, 7/58). Single nucleotide polymorphisms (SNP) were identified at 11 locations in the PVL genes. SNP (nucleotide 1396, A→G) and SNP (nucleotide 1546, A→G) were observed in >10 sequences. Four additional SNP were non-synonymous. Both SNP (nucleotide 16, C→A) and SNP (nucleotide 62, C→T) were present in the same ST59 strain. SNP (nucleotide 527, A→G) was present in five strains belonging to ST30, 121, 1, and 93. SNP (nucleotide 1436, A→C) was present in one ST30 strain. Fifteen strains belonging to ST910, ST217, and ST30 carried a PVL phage that had an icosahedral head morphology. Nine ST59 strains carried ϕ108PVL. Three ST88 strains carried a PVL phage that had an elongated head morphology. Twenty-seven strains, including 60.9% (14/23) of ST59 and all ST338 strains, had no detectable phage. In conclusion, sequence variation in PVL genes and PVL-encoding phages was generally related to the lineage. ST59 strains may indeed carry novel PVL phages.

[Molecular characteristics of methicillin resistant Staphylococcus aureus isolated from Chinese children].

OBJECTIVE: To investigate the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates from Chinese children in seven cities. METHOD: A total of 134 MRSA isolates were collected from nine hospitals. Multilocus sequence typing and spa typing were analyzed by polymerase chain reaction (PCR), and staphylococcal chromosomal cassette mec (SCCmec) type was analyzed by multiplex PCR. The Panton-Valentine leukocidin (pvl) gene was also detected. RESULT: Most MRSA strains were isolated from pneumonia and skin and soft tissue infection (SSTIs) patients, accounting for 82.1%. Overall, 16 sequence types (STs) were obtained, and CC59 (51.7%) was found to be the most prevalent, which included ST 59 and ST 338, followed by ST239 (16.4%). SCCmec types II, III, IV, and V were also identified in the current study. SCCmec type IV was the most predominant type at 50.0%, followed by SCCmec type V at 23.9% and III at 23.9%. SCCmec subtypes IVa, IVc, and IVg were found among SCCmec type IV strains, whereas IVa was the main subtype at 77.6%. Twenty-six spa types were also identified, among which the predominant type was t437 (47.8%). The prevalence of pvl genes and the SCCmec type of strain was relevant, and the pvl gene positive rate was higher in SCCmec type IV and V-type strains than in SCCmec type II and III strains (58.6% vs. 14.3%, P < 0.05); there was a significant difference between them. In the strains isolated from pneumonia and SSTIs, ST59-MRSA-IVa(t437) was the predominant clone. There were five clones detected from the strains isolated from septicemia, with ST59-MRSA-IVa(t437) and ST59-MRSA-V(t437) as the main clones (57.1%). Various predominant clones existed in different regions. ST59-MRSA-IVa(t437) was the prevalent clone in the Guangzhou, Beijing, Chongqing, and Shenzhen areas, whereas ST239-MRSA-III(t037) was the prevalent clone in the Shanghai area. Fifty percent of the isolates from the Wenzhou area belonged to ST910-MRSA-V(t318), whereas three clinical strains isolated from the Shenyang region belonged to three different types. CONCLUSION: The results indicate that MRSA isolates from Chinese children are largely associated with the ST59-MRSA-IV(t437) and ST239-MRSA-III(t037) clones. These two may belong to community-acquired MRSA and hospital-acquired ones, respectively. Different prevalent clones were detected in different diseases and different regions. Therefore, there is a need to conduct further research on clinical isolates, which can guide the choice of antibiotic treatment and the examination of MRSA prevalence.

Susceptibility to and resistance determinants of fusidic acid in Staphylococcus aureus isolated from Chinese children with skin and soft tissue infections.

This study aims to determine the resistance rates and determinants of fusidic acid among Staphylococcus aureus isolates collected from Chinese pediatric patients with skin and soft tissue infections (SSTIs). Between 2008 and 2009, a total of 186 clinical S. aureus isolates were collected from the pediatric patients with SSTIs, abscess (44.6%) was the most common SSTI in children 0-16 years old. Four clinical isolates (4/186, 2.2%) were resistant to fusidic acid. Two of these isolates were methicillin-resistant S. aureus (MRSA) that carry the fusC gene. The other two isolates were methicillin-sensitive S. aureus (MSSA) that carry the fusB gene. In the two fusB-positive clinical isolates, the fusB gene was located in a transposon-like element that has 99% identity with a pUB101 fragment from S. aureus. The four fusidic acid-resistant clinical isolates were ST1-MRSA-SCCmecV-t127, ST93-MRSA-SCCmecIII-t202, ST680-MSSA-t5415, and ST680-MSSA-t377. The fusidic acid resistance rate of S. aureus isolated from Chinese pediatric patients with SSTIs was low, and the genes fusB and fusC were the main resistance determinants. The transposon-like element that contains the fusB gene might participate in the transmission of fusidic acid resistance genes. This is the first report regarding the emergence of fusidic acid-resistant clinical S. aureus isolates in mainland China.

Superantigen gene profiles and presence of exfoliative toxin genes in community-acquired meticillin-resistant Staphylococcus aureus isolated from Chinese children.

This study aimed to evaluate the distribution of superantigen gene profiles and the presence of exfoliative toxin genes in community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) isolated from Chinese children, and simultaneously to assess virulence gene profiles and genetic background. Of the CA-MRSA isolates, 88.9 % (88/99) harboured toxin genes, with sek as the most frequent toxin gene (62.6  %), followed by seq (61.6  %), seb (60.6  %) and sea (35.4  %). The eta gene was detected only in one ST398-IVa-spa t034 strain. The sed and etd genes were not found in any of the isolates tested. A total of 38 virulence genotypes were observed, of which the genotype seb-sek-seq (27.3  %, 24/88) comprised the majority, followed by sea-seb-sek-seq (18.2  %, 16/88). The enterotoxin gene cluster including seg-sei-sem-sen-seo-seu predominated at a rate of 15.1  %. The relationship among toxin genotypes, toxin genes encoding profiles of mobile genetic elements and genetic background was analysed. Among 66 clonal complex (CC) 59 isolates, 87.9 % (58/66) were positive for toxin genes, and 75.8  % (50/66) harboured the toxin gene combination seb-sek-seq. Among seb-sek-seq-positive CC59 strains, 42.0  % (21/50) also carried the sea gene. CC59 corresponded exclusively to accessory gene regulator 1 (agr-1). The data presented here enhance our current knowledge on the virulence determinants of CA-MRSA.

Community-acquired, methicillin-resistant Staphylococcus aureus isolated from children with community-onset pneumonia in China.

Community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) has been associated with morbidity and mortality in various countries. In this study, we characterized the molecular and clinical features of pediatric CA-MRSA pneumonia in China. Between June 2006 and February 2008, 55 previously healthy children confined in eight hospitals countrywide were found to be afflicted with CA-MRSA pneumonia. A total of 55 strains collected from these children were analyzed by multilocus sequence typing (MLST), Staphylococcus cassette chromosome mec (SCCmec) typing, and spa typing. The Panton-Valentine leukocidin (PVL) gene was also detected. Overall, nine STs were obtained, with ST59 (40.4%) established to be the most prevalent type. We first registered the new ST1409 from a child with necrotizing pneumonia. SCCmecIVa was the most predominant type, followed by SCCmec type V. Twelve spa types were identified, of which one new spa type, t5348, was first detected and registered. One typical livestock-associated spa type, t034, was found in a 4-month-old girl living in the countryside. We also found that 40% of those isolates were PVL-positive. In addition, the median age of the children in this study was 10 months. A total of 69% (38/55) of the children with community-acquired pneumonia (CAP) had preceding influenza or influenza-like illness, and three ST910-MRSA-IV strains (PVL gene-positive) were associated with severe necrosis. The results indicated that the recent CA-MRSA found in Chinese children with CAP was largely associated with the spread of the ST59-MRSA-IV clone, and most of the PVL-positive strains in this study did not cause necrotic cases.

Epidemiology and molecular characteristics of community-associated methicillin-resistant and methicillin-susceptible Staphylococcus aureus from skin/soft tissue infections in a children's hospital in Beijing, China.

To evaluate the epidemiology and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children with skin and soft tissue infections (SSTIs) in Beijing, China, prospective community-acquired S. aureus SSTIs surveillance was conducted at the Beijing Children's Hospital, Beijing, China, for a 12-month period from August 1, 2008, to July 30, 2009. Susceptibility to 12 antimicrobials was determined by the agar dilution method. Genotypic characteristics of CA-MRSA isolates were tested by SCCmec typing, spa typing, and multilocus sequence typing. Panton-Valentine leukocidin gene was detected. Of 1104 cases, 31.8% (351) were community-acquired S. aureus. CA-MRSA accounted for 4% (14) of S. aureus. Among 14 CA-MRSA and 120 MSSA isolates tested, 100% and 91.7% were multidrug resistant, respectively. ST59-MRSA-IVa-t437 (42.9%) was the most common form of CA-MRSA. Spa typing analysis of 120 MSSA isolates was performed, followed by pulsed-field gel electrophoresis and multilocus sequence typing of a selected number of isolates. The most common spa types among MSSA were t084 (8.3%), t091 (5.8%), t034 (5%), t127 (4.2%), t002 (4.2%), and t796 (4.2%). No predominant spa type was seen. Of the MSSA isolates that could be classified into spa-CCs, 15.0% had a genetic background observed in CA-MRSA clones (spa-CC437, spa-CC342, and spa-CC377). Panton-Valentine Leukocidin (PVL)-positive community-acquired S. aureus strains were more commonly associated with skin abscesses than other SSTIs (29.4% versus 5.9%, P < 0.01).In conclusion, CA-MRSA infections are not common among Chinese children with SSTIs. Our findings show that MSSA strains in China have diverse genetic backgrounds.

Molecular characteristics of community-acquired, methicillin-resistant Staphylococcus aureus isolated from Chinese children.

The aim of this study was to investigate the molecular characteristics of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates from Chinese children. Ninety-nine isolates were collected from eight hospitals, and analyzed by multilocus sequence typing, staphylococcal chromosomal cassette mec (SCCmec) type, and spa typing. The Panton-Valentine leukocidin (PVL) gene was also detected. Overall, 14 sequence types (STs) were obtained, and ST59 (58.6%) was found to be the most prevalent, followed by ST1 (8%) and ST338 (8%). We also first registered the new ST1409. SCCmec type IV was the most predominant type at 67.7%, followed by SCCmec type V at 32.3%. SCCmec subtypes IVa, IVc, and IVg were found among the SCCmec type IV strains. Twenty-one spa types were also identified. Four new spa types were found by synchronization with the Ridom SpaServer and referring to the website (http://www.SeqNet.org). ST59-MRSA-IVa with t437 accounted for 40.4% of occurrences, making it the most prevalent clone. The prevalence of PVL genes was 58.6%, and multidrug resistance was observed in 95% of all isolates. This result indicates that CA-MRSA isolates in Chinese children are largely associated with the ST59-MRSA-IV clone, and that the predominant clones of CA-MRSA are spread all over the country.