Publications by authors named "Mayuko Saito"

97 Publications

Prolonged viral clearance of severe acute respiratory syndrome coronavirus 2 in the older aged population.

J Infect Chemother 2021 Mar 11. Epub 2021 Mar 11.

Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address:

Introduction: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) is the standard method for the diagnosis of coronavirus disease 2019 (COVID-19). This PCR test can be positive even in patients who have recovered from the disease, and the duration for achieving viral clearance has not been clarified yet.

Methods: This study was conducted between April 3, 2020, and June 17, 2020, at the Toyama University Hospital and the Toyama Rehabilitation Home. We collected the data of patients with COVID-19, analyzing the duration until twice-consecutive negative qRT-PCR test.

Results: A total of 42 patients were enrolled. The median duration of the twice-consecutive negative qRT-PCR test was 29.0 d (interquartile range: 25.75-35.25). The longest duration of viral shedding was 73 d. The duration of viral clearance was significantly longer in the older (>65 years) group than in the younger group (34.5 d vs. 25.0 d, P < 0.0001).

Conclusion: This study demonstrated that viral clearance tends to be sustained in the older adults.
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http://dx.doi.org/10.1016/j.jiac.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951882PMC
March 2021

Familial Clusters of Coronavirus Disease in 10 Prefectures, Japan, February-May 2020.

Emerg Infect Dis 2021 03;27(3):915-918

The overall coronavirus disease secondary attack rate (SAR) in family members was 19.0% in 10 prefectures of Japan during February 22-May 31, 2020. The SAR was lower for primary cases diagnosed early, within 2 days after symptom onset. The SAR of asymptomatic primary cases was 11.8%.
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http://dx.doi.org/10.3201/eid2703.203882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920650PMC
March 2021

Early warning of COVID-19 via wastewater-based epidemiology: potential and bottlenecks.

Sci Total Environ 2021 May 21;767:145124. Epub 2021 Jan 21.

Department of Frontier Sciences for Advanced Environment, Graduate School of Environmental Studies, Tohoku University, Aoba 6-6-06, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan; Department of Civil and Environmental Engineering, Graduate School of Engineering, Tohoku University, Aoba 6-6-06, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan. Electronic address:

An effective early warning tool is of great administrative and social significance to the containment and control of an epidemic. Facing the unprecedented global public health crisis caused by COVID-19, wastewater-based epidemiology (WBE) has been given high expectations as a promising surveillance complement to clinical testing which had been plagued by limited capacity and turnaround time. In particular, recent studies have highlighted the role WBE may play in being a part of the early warning system. In this study, we briefly discussed the basics of the concept, the benefits and critical points of such an application, the challenges faced by the scientific community, the progress made so far, and what awaits to be addressed by future studies to make the concept work. We identified that the shedding dynamics of infected individuals, especially in the form of a mathematical shedding model, and the back-calculation of the number of active shedders from observed viral load are the major bottlenecks of WBE application in the COVID-19 pandemic that deserve more attention, and the sampling strategy (location, timing, and interval) needs to be optimized to fit the purpose and scope of the WBE project.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825884PMC
May 2021

Gene signature of children with severe respiratory syncytial virus infection.

Pediatr Res 2021 Jan 28. Epub 2021 Jan 28.

Department of Virology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

Background: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection.

Methods: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes.

Results: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes.

Conclusions: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV.

Impact: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.
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http://dx.doi.org/10.1038/s41390-020-01347-9DOI Listing
January 2021

Penetration of a swallowed fish bone into pulmonary vein: diagnosis and management.

Heliyon 2020 Nov 26;6(11):e05611. Epub 2020 Nov 26.

Department of Education and Support for Regional Medicine, Tohoku University Hospital, Japan.

We present a case of a 71-year-old woman who accidently swallowed a large fish bone that penetrated into the pulmonary vein. She visited the hospital the next day with a complaint of mild chest discomfort with slight pain and fever of 37.4 °C. Contrast-enhanced chest computed tomography (CT) scan revealed a large fish bone with a length of 35 mm impacted in the middle esophagus. The bone had penetrated into the pulmonary vein, causing mediastinitis. Blood tests revealed elevation in the white blood cell count and C-reactive protein level. Because intractable bleeding from pulmonary vein after endoscopic removal can be lethal, endoscopic removal of the fish bone in an operating room under general anesthesia with cardiovascular surgical standby for possible emergency surgery was selected. After endoscopic removal, mediastinal hematoma was absent with a follow-up chest CT scan, and the mediastinitis was treated with intravenous antibiotics. The patient shortly became afebrile with normalized blood test findings. After confirming the normal findings on the follow-up chest CT scan and endoscopic inspection in the next week, she was discharged from the hospital 10 days after hospitalization without any complications. When the swallowed bone penetrates into the major pericardial vessels, unprepared endoscopic removal may result in fatal sequelae such as intractable mediastinal hemorrhage. Urgent consultation with cardiovascular or thoracic surgeons for a possible emergent surgery is needed before endoscopic removal is attempted.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701346PMC
November 2020

Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants.

EClinicalMedicine 2020 Oct 5;27:100561. Epub 2020 Oct 5.

Department of Virology, Tohoku University, Graduate School of Medicine, Sendai, Japan.

Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA (NV-IgA) in breast milk.

Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016-2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs.

Findings: NV-IgA had high positivity rates against different VLPs, especially against GII (89-100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·03) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23-0·37) were observed.

Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.Funding National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695-01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B):19KK0241.
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http://dx.doi.org/10.1016/j.eclinm.2020.100561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536734PMC
October 2020

Genetic analysis of sapoviruses detected in outbreaks and sporadic cases of acute gastroenteritis in Miyagi Prefecture, Japan.

J Clin Virol 2020 11 19;132:104648. Epub 2020 Sep 19.

Department of Virology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

Background: Human sapovirus (SaV) causes sporadic and endemic acute gastroenteritis worldwide. However, little is known about the relationship between the mode of transmission and genetic characteristics of SaV.

Objective: To investigate the molecular characteristics of SaV-associated acute gastroenteritis among sporadic cases, foodborne, and nonfoodborne outbreaks.

Study Design: We performed a systematic review of publications and genetic analysis of SaV in fecal specimens from 98 outpatients with acute gastroenteritis, 32 stool samples from 8 foodborne outbreaks, and 63 stool samples from 23 nonfoodborne outbreaks in Miyagi Prefecture, Japan from 1993 and between 2004 and 2020. Reverse transcription polymerase chain reaction (RT-PCR) was employed for the detection of SaV, and the partial capsid gene was sequenced for genotyping and phylogenetic analysis.

Results: The overall detection rate of SaV in sporadic cases, foodborne, and nonfoodborne outbreaks was 5.8, 1.7, and 4.3%, respectively. Genotypic analysis revealed GI.1 to be the predominant genotype in sporadic cases (31.5%) and nonfoodborne outbreaks (52.1%), whereas it was not detected in foodborne outbreaks. Some outbreaks occurred following sporadic cases with the same genotype.

Conclusions: The distribution of SaV genotypes was different between foodborne outbreaks and other settings. The effective SaV infection control may differ depending on the genomic characteristics.
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http://dx.doi.org/10.1016/j.jcv.2020.104648DOI Listing
November 2020

Development of a novel in vitro assay to evaluate environmental water using an IL-8 reporter cell line.

EXCLI J 2020 21;19:1054-1063. Epub 2020 Jul 21.

Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

The IL-8 luciferase reporter cell line, THP-G8 cells, used in the sensitization test, OECD442E, can respond to a variety of stimuli other than haptens, such as lipopolysaccharide (LPS), other bacterial toxins, and detergents. Considering these characteristics, we examined the ability of the IL-8 luciferase assay using THP-G8 cells to evaluate water pollution. We first stimulated THP-G8 cell with various Toll-like receptor (TLR) agonists and nucleotide-binding oligomerization domain-like receptor (NLR) agonists, and found that TLR1, 2, 4, 5, 6 agonists and NOD 1, 2 agonists significantly augmented IL-8 luciferase activity (IL8LA). Then, we examined the detection threshold of LPS by THP-G8 cells, and found it 0.4 EU/ml. Next, we examined whether THP-G8 cells can differently respond to a variety of sources of environmental water around Sendai, Japan and Manila, Philippine and whether there is a correlation between the IL8LA of different sources of water and their level of endotoxin assessed by the LAL assay. There was a clear trend that the IL8LA was lower in the upper stream and higher in the downstream in both Japan and Philippine. Moreover, there was a strong correlation between the IL8LA of the environmental water and its endotoxin level. Finally, using N-acetyl-L-cysteine, an antioxidant/radical scavenger, and polymyxin B that neutralizes endotoxin, we demonstrated that there was a difference in the suppressive effects by them between the water from Japan and that from Philippine. These data suggest the potential of the IL-8 luciferase assay for evaluating environmental water pollution both quantitatively and qualitatively.
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http://dx.doi.org/10.17179/excli2020-2104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527499PMC
July 2020

Epidemiological and clinical characteristics of children with acute respiratory viral infections in the Philippines: a prospective cohort study.

Clin Microbiol Infect 2020 Sep 17. Epub 2020 Sep 17.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Objectives: Viral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children.

Methods: A cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated.

Results: Overall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.8), human metapneumovirus (2.1, 1.4-3.2), rhinovirus (2.1, 1.8-2.6), and respiratory syncytial virus (1.6, 1.2-1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0-4.9).

Conclusions: We determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections.
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http://dx.doi.org/10.1016/j.cmi.2020.09.017DOI Listing
September 2020

The Active Center of Co-N-C Electrocatalysts for the Selective Reduction of CO to CO Using a Nafion-H Electrolyte in the Gas Phase.

ACS Omega 2020 Aug 3;5(31):19453-19463. Epub 2020 Aug 3.

Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, Ookayama, Meguro-Ku, Tokyo 1528552, Japan.

To contribute a solution for the global warming problem, the selective electrochemical reduction of CO to CO was studied in the gas phase using a [CO(g), Co-N-C cathode | Nafion-H | Pt/C anode, H/water] system without using carbonate solutions. The Co-N-C electrocatalysts were synthesized by partial pyrolysis of precursors in inert gas, which were prepared from various N-bidentate ligands, Co(NO), and Ketjenblack (KB). The most active electrocatalyst was Co-(4,4'-dimethyl-2,2'-bipyridine)/KB pyrolyzed at 673 K, denoted Co-4,4'-dmbpy/KB(673K). A high performance of CO formation (331 μmol h cm, 217 TOF h) at 0.020 A cm with 78% current efficiency was obtained at -0.75 V (SHE) and 273 K under strong acidic conditions of Nafion-H. Characterization studies using extended X-ray absorption fine structure (EXAFS), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy-energy-dispersive X-ray (TEM-EDX), X-ray diffraction (XRD), and temperature-programmed desorption with mass spectrometry (TPD-MS) indicated the active site as Co coordinated with four N atoms bonding the surface of KB, abbreviated Co-N-C structure. A model of the reduction mechanism of CO on the active site was proposed.
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http://dx.doi.org/10.1021/acsomega.0c01510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424585PMC
August 2020

Genetic diversity of species A rotaviruses detected in clinical and environmental samples, including porcine-like rotaviruses from hospitalized children in the Philippines.

Infect Genet Evol 2020 11 17;85:104465. Epub 2020 Jul 17.

Department of Virology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Rotaviruses are the major cause of severe acute diarrhea in infants and young children. Rotaviruses exhibit zoonosis and thereby infect both humans and animals. Viruses detected in urban rivers possibly reflect the presence of circulating viruses in the catchment. The present study investigates the genetic diversity of species A rotaviruses detected from river water and stool of hospitalized children with acute diarrhea in Tacloban City, the Philippines. Species A rotaviruses were detected by real-time RT-PCR and their genotypes were identified by multiplex PCR and sequencing of partial regions of VP7 and VP4. Rotaviruses were detected in 85.7% (30/35) of the river water samples and 62.7% (151/241) of the clinical samples. Genotypes of VP7 in the river water samples were G1, G2, G3, G4, G5, and G9, and those of VP4 were P[3], P[4], P[6], P[8], and P[13]. Genotypes of viruses from the clinical samples were G2P[4], G1P[8], G3P[8], G4P[6], G5P[6], and G9P[8]. Among those, G2P[4] in clinical samples (77.9%, 81/104) and P[4] of VP4 in river water samples (67.5%, 56/83)) were the most frequently detected rotavirus genotypes. However, G5 was the more frequently detected than G2 in the river water samples (42% vs. 13%) which may be originated from porcine rotavirus. Sequence analyses of eleven gene segments revealed one G5P[6] and two G4P[6] rotaviruses in the clinical samples, wherein, several gene segments were closely related to porcine rotaviruses. The constellation of these rotavirus genes suggests the emergence of reassortment between human and porcine rotavirus due to interspecies transmission. Although two commercial rotavirus vaccines are available now, these vaccines are designed to confer immunity against the major human rotaviruses. Constant monitoring of viral variety in populated areas where humans and domestic animals live in close proximity provides vital information related to the diversity of rotaviruses in a human population.
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http://dx.doi.org/10.1016/j.meegid.2020.104465DOI Listing
November 2020

Clusters of Coronavirus Disease in Communities, Japan, January-April 2020.

Emerg Infect Dis 2020 09 10;26(9). Epub 2020 Jun 10.

We analyzed 3,184 cases of coronavirus disease in Japan and identified 61 case-clusters in healthcare and other care facilities, restaurants and bars, workplaces, and music events. We also identified 22 probable primary case-patients for the clusters; most were 20-39 years of age and presymptomatic or asymptomatic at virus transmission.
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http://dx.doi.org/10.3201/eid2609.202272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454082PMC
September 2020

Quantitative and Qualitative Perturbations of CD8 MAITs in Healthy -Infected Individuals.

Immunohorizons 2020 06 4;4(6):292-307. Epub 2020 Jun 4.

Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037.

CD8 T cells are considered important contributors to the immune response against , yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell-specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8Vα7.2CD161 MAITs: MR1 tetramer and MR1 tetramer, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected individuals did not reveal significant differences for MR1 tetramer MAITs. However, gene expression of MR1 tetramer MAITs showed large interindividual diversity and a tuberculosis-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer cells as compared with MR1 tetramer Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer MAITs as well as a difference in phenotype in the rare population of MR1 tetramer MAITs compared with uninfected controls.
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http://dx.doi.org/10.4049/immunohorizons.2000031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543048PMC
June 2020

Urban informal settlements as hotspots of antimicrobial resistance and the need to curb environmental transmission.

Nat Microbiol 2020 06 25;5(6):787-795. Epub 2020 May 25.

Department of Civil and Environmental Engineering, Tufts University, Medford, MA, USA.

Antimicrobial resistance (AMR) is a growing public health challenge that is expected to disproportionately burden lower- and middle-income countries (LMICs) in the coming decades. Although the contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil or food contaminated with human and animal faeces) has been given less attention as a global driver of AMR, especially in urban informal settlements in LMICs-commonly known as 'shanty towns' or 'slums'. These settlements may be unique hotspots for environmental AMR transmission given: (1) the high density of humans, livestock and vermin living in close proximity; (2) frequent antibiotic misuse; and (3) insufficient drinking water, drainage and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades.
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http://dx.doi.org/10.1038/s41564-020-0722-0DOI Listing
June 2020

Recombinant Nontypeable Genotype II Human Noroviruses in the Americas.

Emerg Infect Dis 2020 01;26(1):157-159

We report multiple nontypeable genotype II noroviruses circulating in South America; nucleotides differed by >25% from those of other genotypes. These viruses have been circulating in the Americas for ≈20 years and show recombination with other genotypes. Clues to norovirus natural history can guide development of treatment and prevention plans.
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http://dx.doi.org/10.3201/eid2601.190626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924879PMC
January 2020

Environmental Presence and Genetic Characteristics of Carbapenemase-Producing from Hospital Sewage and River Water in the Philippines.

Appl Environ Microbiol 2020 01 7;86(2). Epub 2020 Jan 7.

Department of Microbiology and Infectious Diseases, Nara Medical University, Kashihara, Japan.

This study aimed to evaluate the prevalence and genetic characteristics of carbapenemase-producing (CPE) in hospital sewage and river water in the Philippines, which has a typical tropical maritime climate. We collected 83 water samples from 7 hospital sewage and 10 river water sites. CPE were identified using CHROMagar mSuperCARBA, and Gram-negative strains were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) or 16S rRNA gene sequencing. Resistance genes in strains were identified using PCR and DNA sequencing, and transferability of carbapenemase genes from the CPE was investigated with conjugation experiments. Genotyping was performed using multilocus sequence typing (MLST) for and Out of 124 isolates, we identified 51 strains as CPE and divided these into 7 species, 11 , 14 spp., 15 spp., and 11 others, including 4 additional species. Conjugation experiments via broth mating and using J53 revealed that 24 isolates can transfer carbapenemase-encoding plasmids. MLST analysis showed that 6 of 11 isolates belonged to clonal complex 10 (CC10). Of 11 strains, 9 unique sequence types (STs) were identified, including ST147. Five types of carbapenemase genes were identified, with the most prevalent being NDM (= 39), which is epidemic in clinical settings in the Philippines. CC10 and ST147, which are often detected in clinical settings, were the dominant strains. In summary, our results indicate that hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups. Carbapenemase-producing (CPE) cause severe health care-associated infections, and their increasing prevalence is a serious concern. Recently, natural ecosystems have been recognized as important reservoirs of antibiotic resistance genes. We investigated the prevalence and genetic characteristics of CPE isolated from the environment (hospital sewage and river water) in the Philippines and found several CPE, including and other species, with different carbapenemases. The most prevalent carbapenemase gene type was NDM, which is endemic in clinical settings. This study revealed that isolates belonging to carbapenemase-producing CC10 and sequence type 147 (ST147), which are often detected in clinical settings, were dominant in the natural environment. Our work here provides a report on the presence and characteristics of CPE in the environment in the Philippines and demonstrates that both hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.
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http://dx.doi.org/10.1128/AEM.01906-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952235PMC
January 2020

Potential underestimation of influenza virus burden in infants.

Lancet Child Adolesc Health 2019 11 3;3(11):751-752. Epub 2019 Sep 3.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address:

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http://dx.doi.org/10.1016/S2352-4642(19)30278-0DOI Listing
November 2019

Use of antibiotics for common illnesses among children aged under 5 years in a rural community in Indonesia: a cross-sectional study.

Trop Med Health 2019 18;47:45. Epub 2019 Jul 18.

1Department of Virology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575 Japan.

Background: The incidence of antimicrobial resistance has been increasing worldwide in the past decades, which includes resistance to bacteria that cause common childhood illnesses, such as acute respiratory infections and diarrhea. Numerous children with those common illnesses are treated with antibiotics. However, in such cases, antibiotic treatment is not required. Community-based studies focusing on antibiotic use among children are still limited. This study aimed to identify the prevalence of antibiotic use for common childhood illnesses and to investigate factors associated with antibiotic use in children under 5 years old as well as female caregivers in a rural community in Indonesia.

Methods: A cross-sectional study of 334 children in three villages of Banten Province, located in the western part of Java Island, was conducted in May 2018. Female caregivers who were responsible for providing medications to children were interviewed. We obtained information such as demographic data, any common clinical illness within the last 30 days, and antibiotic usage during an episode of illness. We excluded children with underlying disease that require a regular follow-up and children who were hospitalized in the last 30 days in the analysis. Antibiotic use answered by female caregivers was verified by checking its package or showing photos of various antibiotics to the female caregivers. Crushed antibiotics were confirmed with health professionals.

Results: A total of 203 children had clinical symptoms, and the most common symptom was fever and respiratory symptoms. In total, 49.3% received antibiotics, and 66% of them were prescribed by private health professionals. Only two children received antibiotics without a prescription. The most common antibiotic used among children was amoxicillin.

Conclusions: The high prevalence of antibiotic use was observed in children under 5 years of age, and the major source to obtain antibiotics was to consult health professionals. Training on appropriate antibiotic use must be conducted for health professionals in not only public but also private sectors.
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http://dx.doi.org/10.1186/s41182-019-0173-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639925PMC
July 2019

Circulating T cell-monocyte complexes are markers of immune perturbations.

Elife 2019 06 25;8. Epub 2019 Jun 25.

Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, United States.

Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.
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http://dx.doi.org/10.7554/eLife.46045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592685PMC
June 2019

Aetiology and risks factors associated with the fatal outcomes of childhood pneumonia among hospitalised children in the Philippines from 2008 to 2016: a case series study.

BMJ Open 2019 03 30;9(3):e026895. Epub 2019 Mar 30.

Virology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: Pneumonia remains the leading cause of hospitalisations and deaths among children aged <5 years. Diverse respiratory pathogens cause acute respiratory infections, including pneumonia. Here, we analysed viral and bacterial pathogens and risk factors associated with death of hospitalised children.

Design: A 9-year case series study.

Setting: Two secondary-care hospitals, one tertiary-care hospital and one research centre in the Philippines.

Participants: 5054 children aged <5 years hospitalised with severe pneumonia.

Methods: Nasopharyngeal swabs for virus identification, and venous blood samples for bacterial culture were collected. Demographic, clinical data and laboratory findings were collected at admission time. Logistic regression analyses were performed to identify the factors associated with death.

Results: Of the enrolled patients, 57% (2876/5054) were males. The case fatality rate was 4.7% (238/5054), showing a decreasing trend during the study period (p<0.001). 55.0% of the patients who died were either moderately or severely underweight. Viruses were detected in 61.0% of the patients, with respiratory syncytial virus (27.0%) and rhinovirus (23.0%) being the most commonly detected viruses. In children aged 2-59 months, the risk factors significantly associated with death included age of 2-5 months, sensorial changes, severe malnutrition, grunting, central cyanosis, decreased breath sounds, tachypnoea, fever (≥38.5°C), saturation of peripheral oxygen <90%, infiltration, consolidation and pleural effusion on chest radiograph.Among the pathogens, adenovirus type 7, seasonal influenza A (H1N1) and positive blood culture for bacteria were significantly associated with death. Similar patterns were observed between the death cases and the aforementioned factors in children aged <2 months.

Conclusion: Malnutrition was the most common factor associated with death and addressing this issue may decrease the case fatality rate. In addition, chest radiographic examination and oxygen saturation measurement should be promoted in all hospitalised patients with pneumonia as well as bacteria detection to identify patients who are at risk of death.
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http://dx.doi.org/10.1136/bmjopen-2018-026895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475207PMC
March 2019

Age-specific incidence rates and risk factors for respiratory syncytial virus-associated lower respiratory tract illness in cohort children under 5 years old in the Philippines.

Influenza Other Respir Viruses 2019 07 19;13(4):339-353. Epub 2019 Mar 19.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Respiratory syncytial virus (RSV) is one of the main viral causes of lower respiratory tract illness (LRTI), especially in young children. RSV vaccines, including maternal and infant vaccines, are under development; however, more epidemiological studies are needed to develop effective vaccination strategies.

Objectives: To estimate detailed age-specific incidence rates and severity of RSV-associated LRTI (RSV-LRTI) using data from a community-based prospective cohort study in the Philippines.

Patients/methods: Cohort children who visited health facilities due to acute respiratory symptoms were identified, and nasopharyngeal swabs were collected to detect RSV. The severity of RSV-LRTI was assessed using the severity definition proposed by the World Health Organization. Risk factors for developing RSV-LRTI and contribution of SpO measurement were also evaluated.

Results: A total of 395 RSV episodes which occurred in children aged 2-59 months were categorised as 183 RSV-LRTI, 72 as severe RSV-LRTI and 29 as very severe RSV-LRTI. Children aged 3-5 months had the highest incidence rate of RSV-LRTI, at 207.4 per 1000 child-years (95% CI: 149.0-279.5). Younger age group, place of living and low educational level of caregivers were associated with developing RSV-LRTI. Clinical manifestations had low levels of agreement with hypoxaemia as measured by pulse oximeter.

Conclusion: The highest burden of RSV was observed in young infants aged 3-5 months, whereas the burden was also high in those aged 12-20 months. Future vaccination strategies should consider the protection of older children, especially those aged one year, as well as young infants.
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http://dx.doi.org/10.1111/irv.12639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586181PMC
July 2019

The association between consuming bivalves, and acute gastroenteritis and norovirus in Tokyo, Japan.

J Med Virol 2019 06 7;91(6):986-996. Epub 2019 Feb 7.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

A prospective matched case-control study was conducted to evaluate associations between dietary histories, including consumption of bivalves, diarrhea, and norovirus positive diarrhea in adult ambulatory patients at an outpatient clinic of a hospital in Tokyo, Japan. Ambulatory cases with diarrhea were matched with nondiarrheal control patients, who visited the same clinic. A standardized questionnaire was used to obtain patients' information, including histories of food consumption and clinical information. Norovirus infection was confirmed using real-time reverse transcription polymerase chain reaction. A total of 207 patients, including 69 diarrheal cases and 138 nondiarrheal cases were included in the analysis. Among them, 60 (29.0%) participants reported consuming bivalves. Norovirus was detected in 35% (24/69) of diarrheal cases. Of those, 10 (41.7%) reported consumption of bivalves and of those, 6 (60.0%) consumed raw bivalves. The proportion of those who consumed raw bivalves was significantly higher in norovirus-positive diarrheal cases than in norovirus-negative diarrheal cases (25.0% vs 6.7%; odds ratio [OR], 4.67; 95% confidence interval [CI], 1.1-20.7) and matched nondiarrheal controls (25.0% vs 6.3%, OR: 5.00; 95% CI, 1.1-22.2). The attributable fraction of consuming raw bivalves for norovirus-associated diarrhea to matched nondiarrheal controls was 20.0%. Consuming raw bivalves was substantially attributed to norovirus-associated diarrhea in adult ambulatory patients and preventive measures for reducing the risk associated with consumption of raw bivalves could decrease the incidence of norovirus-associated diarrhea.
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http://dx.doi.org/10.1002/jmv.25416DOI Listing
June 2019

Gastric Xanthomas and Fundic Gland Polyps as Endoscopic Risk Indicators of Gastric Cancer.

Gut Liver 2019 03;13(4):409-414

Department of Gastroenterology and Hepatology, Sapporo Medical University, Sapporo, Japan.

Background/aims: Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most cases. The aim of this study was to evaluate associations between gastric cancer and these benign lesions.

Methods: Two expert endoscopists reviewed a series of gastroscopy images. FGPs, HPs, and XTs were diagnosed by endoscopic appearance, whereas all gastric cancers were confirmed pathologically.

Results: Of the 1,227 patients reviewed, 114 (9.3%) had a concurrent or past history of gastric cancer. The overall prevalences of FGPs, HPs and XTs were 9.4%, 6.3% and 14.2%, respectively. HPs and XTs coexisted in 1.6% of patients, whereas other combinations were rarer. XTs were observed in 39.3% and 11.5% of patients with and without gastric cancer, respectively (p<0.001). In contrast, no gastric cancer patients had FGPs, whereas 10.4% of patients without cancer had FGPs (p<0.001). The prevalence of HPs was similar between the two groups (8.8% and 6.0% of patients with and without cancer, respectively, p=0.29). Multivariate and Mantel-Haenszel analyses demonstrated that XTs were positively associated and FGPs were negatively associated with gastric cancer.

Conclusions: XTs and FGPs might be useful as endoscopic risk indicators for monitoring gastric cancer.
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http://dx.doi.org/10.5009/gnl17136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622560PMC
March 2019

Complete Genome Sequences of 12 Human Respiratory Syncytial Virus () Strains Detected in Children with Repeated Subgroup B Infections in the Philippines.

Microbiol Resour Announc 2018 Dec 6;7(22). Epub 2018 Dec 6.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Complete genome sequences were determined for 12 human respiratory syncytial virus strains collected from nasopharyngeal samples obtained from children with repeated subgroup B infections. Eight common amino acid polymorphisms in the G, F, and L proteins were identified between the viruses detected in initial and subsequent infections.
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http://dx.doi.org/10.1128/MRA.01017-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284083PMC
December 2018

Association Between Preceding Viral Respiratory Infection and Subsequent Respiratory Illnesses Among Children: A Prospective Cohort Study in the Philippines.

J Infect Dis 2019 01;219(2):197-205

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Acute respiratory infection (ARI) is of great concern in public health. It remains unclear whether viral infections can affect the host's susceptibility to subsequent ARIs.

Methods: A prospective cohort study on ARIs of children below 5 years old was conducted in the Philippines from 2014 to 2016. The respiratory symptoms were recorded daily, and nasopharyngeal swabs were collected at both household and health facilities. The specimens were tested for respiratory viruses. We then determined whether viral etiology was associated with the severity of the present ARI and whether previous viral infections was associated with subsequent ARIs.

Results: A total of 3851 children and 16337 ARI episodes were enrolled and recorded, respectively. Samples were collected from 24% of all ARI episodes; collection rate at the healthcare facilities was 95%. Enterovirus D68, rhinovirus species C, and respiratory syncytial virus were significantly associated with severe ARIs. The risk for subsequent ARIs was significantly enhanced after infections with adenovirus, influenza A virus, parainfluenza virus type 4, and rhinovirus species C.

Conclusions: This study revealed that viral etiology plays a significant role in the severity of the present ARI and that viral infection affects the host's susceptibility to subsequent ARIs.
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http://dx.doi.org/10.1093/infdis/jiy515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306022PMC
January 2019

Distribution of norovirus and sapovirus genotypes with emergence of NoV GII.P16/GII.2 recombinant strains in Chiang Mai, Thailand.

J Med Virol 2019 02 17;91(2):215-224. Epub 2018 Oct 17.

Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Norovirus (NoV) and sapovirus (SaV) are recognized as the causative agents of acute gastroenteritis, and NoV is one of the leading pathogens reported worldwide. This study reports on the distribution of NoV and SaV genotypes in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand, from January 2015 to February 2017. From a total of 843 stool samples, 170 (20.2%) and 16 (1.9%) were identified as having NoV and SaV infections, respectively. Two samples (0.2%) were positive for both NoV and SaV. Of these, NoV GII.4 (57.2%) was the dominant genotype, followed by GII.2, GII.3, GII.17, GII.6, GII.7, GII.13, GII.14, GII.15, GII.21, GI.6, and GI.5. Among the NoV GII.4 variants, Sydney 2012 was the dominant variant during the period 2015-2016, while the other variants detected in this study were Asia 2003 and New Orleans 2009. Interestingly, an increase of NoV GII.2 was observed in 2016 and 2017. Characterization of partial RNA-dependent RNA polymerase and VP1 nucleotide sequences of GII.2 strains revealed that more than half of the GII.2 strains circulating in 2016 and 2017 were recombinant strains of GII.P16/GII.2. For SaV, the majority of strains belonged to GI.1 (55.6%) and GI.2 (33.3%), while GII.5 accounted for 11.1%. In conclusion, this study demonstrates the diversity of NoV and SaV, and the emergence of NoV GII.P16/GII.2 recombinant strains in 2016 and 2017 in Chiang Mai, Thailand.
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http://dx.doi.org/10.1002/jmv.25261DOI Listing
February 2019

Genetic diversity of human sapovirus across the Americas.

J Clin Virol 2018 07 6;104:65-72. Epub 2018 May 6.

Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address:

Background: Sapoviruses are responsible for sporadic and epidemic acute gastroenteritis worldwide. Sapovirus typing protocols have a success rate as low as 43% and relatively few complete sapovirus genome sequences are available to improve current typing protocols.

Objective/study Design: To increase the number of complete sapovirus genomes to better understand the molecular epidemiology of human sapovirus and to improve the success rate of current sapovirus typing methods, we used deep metagenomics shotgun sequencing to obtain the complete genomes of 68 sapovirus samples from four different countries across the Americas (Guatemala, Nicaragua, Peru and the US).

Results: VP1 genotyping showed that all sapovirus sequences could be grouped in the four established genogroups (GI (n = 13), GII (n = 30), GIV (n = 23), GV (n = 2)) that infect humans. They include the near-complete genome of a GI.6 virus and a recently reported novel GII.8 virus. Sequences of the complete RNA-dependent RNA polymerase gene could be grouped into three major genetic clusters or polymerase (P) types (GI.P, GII.P and GV.P) with all GIV viruses harboring a GII polymerase. One (GII.P-GII.4) of the new 68 sequences was a recombinant virus with the hotspot between the NS7 and VP1 regions.

Conclusions: Analyses of this expanded database of near-complete sapovirus sequences showed several mismatches in the genotyping primers, suggesting opportunities to revisit and update current sapovirus typing methods.
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http://dx.doi.org/10.1016/j.jcv.2018.05.003DOI Listing
July 2018

Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines.

J Infect Dis 2018 08;218(7):1045-1053

Department of Virology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.

Background: Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes.

Methods: We conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections.

Results: We examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein.

Conclusions: Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.
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http://dx.doi.org/10.1093/infdis/jiy256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107742PMC
August 2018