Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

Treatment intensity and characteristics of MRSA infection in CF.

BACKGROUND: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and interchange of hospital-associated strains carrying the staphylococcal chromosomal cassette mec-II (SCCmec-II) with those in the community (SCCmec-IV) has increased. This study assesses the impact of MRSA and different MRSA types on clinical outcomes, medication use, and antibiotic sensitivities. METHODS: MRSA isolates from CF patients at our center were typed by SCCmec- and pv(l) status. Patient characteristics, lung function and nutrition are compared between MRSA types and to age, gender and Pseudomonas aeruginosa matched patients with chronic methicillin sensitive S. aureus (MSSA) infection. RESULTS: Seventy-two percent of patients carry pv(l) negative SCCmec-II isolates. Seventeen percent of all MRSA were SCCmec-IV pv(l) positive (USA300). These patients were younger and fewer had chronic P. aeruginosa infection, whereas pv(l)-negative SCCmec-IV isolates show highest antibiotic resistance. Nutritional outcomes and FEV1 percent predicted (75.1 ± 2.7 versus 77.9 ± 2.7) did not differ in patients with MRSA compared to those with MSSA but MRSA patients received more pulmonary maintenance but not oral antibiotic medications. CONCLUSION: Patients with chronic MRSA are treated more intensely than age, gender and Pseudomonas aeruginosa matched MSSA-positive patients but clinical characteristics within MRSA patients vary depending on MRSA types.

Prevalence and risk factor analysis for methicillin-resistant Staphylococcus aureus nasal colonization in children attending child care centers.

Children attending child care centers (CCCs) are at increased risk for infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Nasal colonization often precedes infection, and MRSA colonization has been associated with increased infection risk. Community-associated MRSA (CA-MRSA) has caused increased MRSA infections in the general population, including children. Little is known about the frequency of MRSA nasal colonization in young children, particularly in those attending CCCs where disease transmission is common. We sampled the nares of 1,163 children in 200 classrooms from 24 CCCs in North Carolina and Virginia to assess S. aureus colonization. MRSA strains were molecularly analyzed for staphylococcal cassette chromosome mec (SCCmec) type, Panton-Valentine leukocidin status, and multilocus sequence type. A case-control study was performed to identify risk factors for MRSA colonization. We found that 18.1% children were colonized with S. aureus and 1.3% with MRSA. Molecular analysis of the MRSA strains identified 47% as CA-MRSA and 53% as health care-associated MRSA (HA-MRSA). Although two centers had multiple children colonized with MRSA, genotyping indicated that no transmission had occurred within classrooms. The case-control study did not detect statistically significant risk factors for MRSA colonization. However, MRSA-colonized children were more likely to be nonwhite and to have increased exposure to antibiotics and skin infections in the home. Both CA-MRSA and HA-MRSA strains were found colonizing the nares of children attending CCCs. The low frequency of colonization observed highlights the need for a large multicenter study to determine risk factors for MRSA colonization and subsequent infection in this highly susceptible population.

Prevalence of community-associated methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis.

We prospectively determined the prevalence of community-associated Staphylococcus aureus in a large cystic fibrosis (CF) center between October 2005 and October 2007. We found that 2.7% (19/707) of the CF patients who had cultures during the study period were infected with this organism, representing 14% of the total methicillin-resistant Staphylococcus aureus strains (n = 140) recovered from the patient population during the study period.

Comparison of culture and 2 real-time polymerase chain reaction assays to detect group B Streptococcus during antepartum screening.

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates but is preventable if the mother is diagnosed before and treated at delivery. Using 200 vaginal-rectal swabs inoculated to enrichment (LIM) broths, we compared routine culture and 2 real-time polymerase chain reaction (PCR) assays for detection of GBS: the LightCycler (LC) Strep B analyte-specific reagents (ASRs) (Roche Diagnostics, Indianapolis, IN) and the BD GeneOhm StrepB (BD-StrepB) test (BD GeneOhm Sciences, San Diego, CA). Culture detected 26.5% GBS-positive specimens, whereas the LC Strep B ASR and BD-StrepB test identified 29.5% and 30.0% positive specimens, respectively. Because of the increased detection rate of 3.0% to 3.5% observed with PCR, a second GBS-specific amplicon was sequenced to confirm the presence of GBS that was not detected by culture. In our hands, the sensitivity/specificity of the LC Strep B ASR was 100%/95.9%, and the BD-StrepB test was 92.5%/92.5% using culture as the gold standard.

Comparison of Cepheid's analyte-specific reagents with BD directigen for detection of respiratory syncytial virus.

For detection of respiratory syncytial virus (RSV), the BD Directigen RSV rapid antigen assay was compared to Cepheid's real-time reverse transcriptase PCR RSV analyte-specific reagents. The Directigen RSV assay resulted in a 23% false-negative rate, using PCR and chart review as the gold standard, indicating that rapid RSV PCR results would be advantageous.

Hrb27C, Sqd and Otu cooperatively regulate gurken RNA localization and mediate nurse cell chromosome dispersion in Drosophila oogenesis.

Heterogeneous nuclear ribonucleoproteins, hnRNPs, are RNA-binding proteins that play crucial roles in controlling gene expression. In Drosophila oogenesis, the hnRNP Squid (Sqd) functions in the localization and translational regulation of gurken (grk) mRNA. We show that Sqd interacts with Hrb27C, an hnRNP previously implicated in splicing. Like sqd, hrb27C mutants lay eggs with dorsoventral defects and Hrb27C can directly bind to grk RNA. Our data demonstrate a novel role for Hrb27C in promoting grk localization. We also observe a direct physical interaction between Hrb27C and Ovarian tumor (Otu), a cytoplasmic protein implicated in RNA localization. We find that some otu alleles produce dorsalized eggs and it appears that Otu cooperates with Hrb27C and Sqd in the oocyte to mediate proper grk localization. All three mutants share another phenotype, persistent polytene nurse cell chromosomes. Our analyses support dual cooperative roles for Sqd, Hrb27C and Otu during Drosophila oogenesis.