Molecular Evolution of GII.P31/GII.4_Sydney_2012 Norovirus over a Decade in a Clinic in Japan.

Norovirus (NoV) genogroup II, polymerase type P31, capsid genotype 4, Sydney_2012 variant (GII.P31/GII.4_Sydney_2012) has been circulating at high levels for over a decade, raising the question of whether this strain is undergoing molecular alterations without demonstrating a substantial phylogenetic difference. Here, we applied next-generation sequencing to learn more about the genetic diversity of 14 GII.P31/GII.4_Sydney_2012 strains that caused epidemics in a specific region of Japan, with 12 from Kyoto and 2 from Shizuoka, between 2012 and 2022, with an emphasis on amino acid (aa) differences in all three ORFs. We found numerous notable aa alterations in antigenic locations in the capsid region (ORF2) as well as in other ORFs. In all three ORFs, earlier strains (2013-2016) remained phylogenetically distinct from later strains (2019-2022). This research is expected to shed light on the evolutionary properties of dominating GII.P31/GII.4_Sydney_2012 strains, which could provide useful information for viral diarrhea prevention and treatment.

Complement receptor type 1 and 2 (CR1 and CR2) gene polymorphisms and plasma protein levels are associated with the Dengue disease severity.

The pathological outcome of dengue disease results from complex interactions between dengue virus (DENV) and host genetics and immune response. Complement receptor types 1 and 2 (CR1 and CR2) mediate complement activation through the alternative pathway. This study investigated the possible association of genetic polymorphisms and plasma levels of CR1 and CR2 with dengue disease. A total of 267 dengue patients and 133 healthy controls were recruited for this study. CR1 and CR2 gene polymorphisms were analyzed by Sanger sequencing, while plasma CR1 and CR2 levels were measured by ELISA. The frequency of the CR1 minor allele rs6691117G was lower in dengue patients and those with severe dengue compared to healthy controls. Plasma CR1 and CR2 levels were decreased in dengue patients compared to healthy controls (P < 0.0001) and were associated with platelet counts. CR1 levels were lower in dengue patients with warning signs (DWS) compared to those without DWS, while CR2 levels were decreased according to the severity of the disease and after 5 days (T1) and 8 days (T2) of follow-up. CR2 levels were decreased in dengue patients positive for anti-DENV IgG and IgM and patients with bleeding and could discriminate DWS and SD from dengue fever patients (AUC = 0.66). In conclusion, this study revealed a reduction in CR2 levels in dengue patients and that the CR1 SNP rs6691117A/G is associated with the dengue severity. The correlation of CR2 levels with platelet counts suggests that CR2 could be an additional biomarker for the prognosis of severe dengue disease.

Whole genome sequencing and genomic characterization of a DS-1-like G2P[4] group A rotavirus in Japan.

After rotavirus was discovered in 1973, it became the leading pathogen in causing acute gastroenteritis in humans worldwide. In this study, we performed whole genome sequencing and genomic characterization of a DS-1-like G2P[4] group A rotavirus in feces of a Japanese child with acute gastroenteritis who was fully Rotarix® vaccinated. The genomic investigation determined a genomic constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 of this rotavirus strain. Its antigenic epitopes of the VP7 and VP4 proteins had significant mismatches compared with the vaccine strains. Our study is the latest attempt to investigate the evolution of the VP7 and VP4 genes of emerging G2P[4] rotavirus in Japan.

A Comparative Study of Acute Gastroenteritis Symptoms in Single- versus Multiple-Virus Infections.

Many different enteric viruses can cause acute gastroenteritis in humans worldwide. While a single virus can indeed cause disease, multiple-virus infections are commonly reported. However, data regarding a comparison between single- and multiple-virus infections upon clinical manifestations of acute gastroenteritis are relatively limited. In this study, a total of 2383 fecal specimens were collected from children with acute gastroenteritis during June 2014-July 2017 in a pediatric clinic in Japan and tested for 11 viruses by multiplex RT-PCR. At least 1 virus was found in 1706 (71.6%) specimens and norovirus GII was the most frequent agent, followed by rotavirus A and other viruses. Multiple-virus infections were identified in 565 cases (33.1%). While major clinical symptoms were found to be significantly different in some single- vs. multiple-virus infections, the disease severity was statistically non-significant. Our study highlights the burden of multiple-virus infections for acute gastroenteritis and the clinical features of patients with multiple-virus infections.

Nonstationary footprints of ENSO in the Mekong River Delta hydrology.

The Mekong River Delta (MRD) is an essential agricultural area for the worldwide rice supply. Floods and droughts triggered by El Niño southern oscillation (ENSO) have been threatening sustenance in the MRD. Sustainable food supplies require understanding the response of the MRD hydrology to the changing ENSO behaviour in recent decades. Here, we reconstructed the annual rainfall maxima in the MRD using the oceanic paleoclimate proxy from coral skeletons and compared them with ENSO indexes. Annual minima of coral-based seawater oxygen isotope (δ18Osw) correlated with annual rainfall maxima, which allowed to extend rainfall data from 1924 to the recent. The annual rainfall maxima based on δ18Osw negatively correlated with the central Pacific El Niño index. This suggested that La Niña and central Pacific El Niño events lead to heavy and light rainy seasons. The heavy rainy season had more serious impacts in recent decades, which likely increases the flood risk. In contrast, the frequency and rainfall amount of the light rainy season has not changed significantly, although a catastrophic drought has hit the MRD. Our finding concludes that the impact of the ENSO event on MRD hydrology is inconsistent in the past century.

Genomic characterization of SARS-CoV-2 from vaccine breakthrough cases in Allegheny County, Pennsylvania.

We performed whole genome sequencing on SARS-CoV-2 from 59 vaccinated individuals from southwest Pennsylvania who tested positive between February and September, 2021. A comparison of mutations among vaccine breakthrough cases to a time-matched control group identified potential adaptive responses of SARS-CoV-2 to vaccination.

Whole genome sequencing and evolutionary analysis of G8P [8] rotaviruses emerging in Japan.

Unusual DS-1-like intergenogroup reassortant rotaviruses with a bovine-like G8 genotype (DS-1-like G8P [8] rotaviruses) have emerged and rapidly spread in several countries. In this study, the nucleotide sequences of seven human rotavirus G8P [8] strains in 2017 and 2019 in Japan were determined using viral metagenomics. Its genomic constellation (VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes) was defined as G8-P [8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Our genetic analysis revealed that the Japanese G8P [8] rotavirus strains in 2017 and 2019 were classified into the same lineages G8-5 and P [8]-3, but they were phylogenetically located on separate branches and belonged to distinct clusters. Our study is the first attempt to investigate the evolution of emerging rotavirus G8P [8] in Japan.

Detection of Enterococcus avium in a case of urinary tract infection and haematuria.

Enterococci have been recognized as major pathogens causing nosocomial and community-acquired infections. The emergence of antimicrobial-resistant enterococci is one of the major public health challenges worldwide. While many enterococcal species have been identified, Enterococcus avium is rarely detected in humans. Here we present an interesting case of urinary tract infection and haematuria involving E. avium in a 72-year-old patient. The patient underwent antibiotic therapy and surgical procedures with excellent improvement. This case report highlights the important role of E. avium in clinical settings.

Predictive model for severe COVID-19 using SARS-CoV-2 whole-genome sequencing and electronic health record data, March 2020-May 2021.

OBJECTIVE: We used SARS-CoV-2 whole-genome sequencing (WGS) and electronic health record (EHR) data to investigate the associations between viral genomes and clinical characteristics and severe outcomes among hospitalized COVID-19 patients. METHODS: We conducted a case-control study of severe COVID-19 infection among patients hospitalized at a large academic referral hospital between March 2020 and May 2021. SARS-CoV-2 WGS was performed, and demographic and clinical characteristics were obtained from the EHR. Severe COVID-19 (case patients) was defined as having one or more of the following: requirement for supplemental oxygen, mechanical ventilation, or death during hospital admission. Controls were hospitalized patients diagnosed with COVID-19 who did not meet the criteria for severe infection. We constructed predictive models incorporating clinical and demographic variables as well as WGS data including lineage, clade, and SARS-CoV-2 SNP/GWAS data for severe COVID-19 using multiple logistic regression. RESULTS: Of 1,802 hospitalized SARS-CoV-2-positive patients, we performed WGS on samples collected from 590 patients, of whom 396 were case patients and 194 were controls. Age (p = 0.001), BMI (p = 0.032), test positive time period (p = 0.001), Charlson comorbidity index (p = 0.001), history of chronic heart failure (p = 0.003), atrial fibrillation (p = 0.002), or diabetes (p = 0.007) were significantly associated with case-control status. SARS-CoV-2 WGS data did not appreciably change the results of the above risk factor analysis, though infection with clade 20A was associated with a higher risk of severe disease, after adjusting for confounder variables (p = 0.024, OR = 3.25; 95%CI: 1.31-8.06). CONCLUSIONS: Among people hospitalized with COVID-19, older age, higher BMI, earlier test positive period, history of chronic heart failure, atrial fibrillation, or diabetes, and infection with clade 20A SARS-CoV-2 strains can predict severe COVID-19.

Whole genome sequence of an uncommon G9P[4] species A rotavirus containing DS-1-like (genotype 2) genes in Japan.

Species A rotaviruses (RVAs) have been recognized as one of the leading causes of acute gastroenteritis in humans worldwide. Here, the complete coding sequences of 11 RNA segments of an uncommon G9P[4] RVA strain, which was detected in feces of a diarrheal child in Japan, were determined by next-generation sequencing technology. Its genomic constellation, VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, was determined as G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. This work reports the complete coding sequences of a G9P[4] RVA strain containing DS-1-like (genotype 2) genes that was isolated in Japan in 2013.

Evaluation of Viral Loads in Patients With SARS-CoV-2 Delta Variant Infection: Higher Loads Do Not Translate Into Different Testing Scenarios.

The Delta SARS-CoV-2 variant is very infectious, and it is spreading quickly during this pandemic. In the study, we compared viral loads estimated by means of the Ct values emerging from RT-PCR swab tests in surging cases infected with the SARS-CoV-2 Delta variant in the fourth wave of COVID-19 with the three prior waves. The data comprised viral loads from positive cases detected within the UPMC health care system in Allegheny County, Pennsylvania. A total of 2059 upper airway samples were collected and tested for SARS-CoV-2 positive by RT-PCR during March 2020 to September 2021. We did not observe significant difference in viral load difference between the third (December 2020 to January 2021) and fourth (June 2021 to September 2021) waves; however, they had the higher viral load than the first (March 2020 to June 2020) and second waves (June 2020 to August 2020). We did find an age-related effect with the elderly presenting with lower viral loads, which was also seen in the earlier waves. However, the level of the viral loads in the fourth wave in the respect of the previous ones was not sufficiently increased to change our testing strategies by means of increased use of rapid antigen tests (RAT).

Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 test for bronchoalveolar lavage.

Accurate and rapid laboratory tests are essential for the prompt diagnosis of COVID-19, which is important to patients and infection control. The Xpert Xpress SARS-CoV-2 test is a real-time RT-PCR intended for the qualitative detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens. In this study, we assessed the analytical performance characteristics of this rapid test for SARS-CoV-2 in 60 bronchoalveolar lavage (BAL) specimens. BAL is a specimen type that is not authorized under EUA for the Xpert Xpress SARS-CoV-2 test. The limit of detection of the Xpert Xpress SARS-CoV-2 test was 500 copies/ml. The overall agreement of the Xpert Xpress SARS-CoV-2 test was 100%. The Xpert Xpress SARS-CoV-2 test is sensitive and specific to aid in diagnosis of COVID-19 using bronchoalveolar lavage.

Pasteurella multocida bacteremia in a patient with septic arthritis.

Pasteurella multocida is a common commensal microorganism found in the nasopharynx of domestic and wild animals. Humans acquire P multocida infection primarily through contact with animals or their mucous secretions. P multocida is infrequently encountered in clinical settings, and it is considered as a zoonotic pathogen. In this study, we present an interesting case of septic arthritis and bacteremia caused by P multocida in a 62-year-old patient. The patient was treated with surgical procedures and antibiotic therapy, which made significant improvement. This case study highlights the importance of P multocida in causing zoonotic infection in humans.

Keratitis caused by Nocardia farcinica in a contact lens wearer.

Bacterial keratitis is an infection of the cornea. This kind of infection can progress quickly and if left untreated, it can eventually cause complete blindness. While Staphylococcus aureus and Pseudomonas aeruginosa are most commonly responsible for this type of infection in the United States, Nocardia spp. is rarely encountered. Here we describe an interesting case of Nocardia farcinica keratitis in a 31-year-old male patient having an extended wear of contact lenses. The patient presented at the emergency department with irritation, foreign body sensation, redness, and pain of his left eye. Nocardia farcinica was isolated from a corneal scraping specimen, and determined by sequencing a region of 16S rRNA gene. The patient had antimicrobial therapy with good improvement. We highlight the important role of Nocardia farcinica in causing keratitis, and its accurate and timely diagnosis is needed to avoid poor visual outcomes.

Secondary syphilis as an initial presentation of HIV.

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, generally presents in distinct stages that sequentially progress in a predictable pattern. However, in the case of syphilis and HIV coinfection, the progression of the disease may be atypical, and syphilis may be the initial presentation of an underlying HIV infection in an undiagnosed patient. These patients can initially present with symptoms of secondary syphilis and can have a rapid and aggressive initial course. Here we describe a case of syphilis in a patient who presented in the secondary stage with a diffuse maculopapular rash, who was later found to have an underlying HIV coinfection.