-
JMIR Public Health and Surveillance May 2024The early identification of outbreaks of both known and novel influenza-like illnesses is an important public health problem.
BACKGROUND
The early identification of outbreaks of both known and novel influenza-like illnesses is an important public health problem.
OBJECTIVE
The design and testing of a tool that detects and tracks outbreaks of both known and novel influenza-like illness, such as the SARS-CoV-19 worldwide pandemic, accurately and early.
METHODS
This paper describes the ILI Tracker algorithm that first models the daily occurrence of a set of known influenza-like illnesses in hospital emergency departments in a monitored region using findings extracted from patient care reports using natural language processing. We then show how the algorithm can be extended to detect and track the presence of an unmodeled disease which may represent a novel disease outbreak.
RESULTS
We include results based on modeling the diseases influenza, respiratory syncytial virus, human metapneumovirus, and parainfluenza for five emergency departments in Allegheny County Pennsylvania from June 1, 2014 through May 31, 2015. We also include the results of detecting the outbreak of an unmodeled disease, which in retrospect was very likely an outbreak of the enterovirus EV-D68.
CONCLUSIONS
The results reported in this paper provide support that ILI Tracker was able to track well the incidence of four modeled influenza-like diseases over a one-year period, relative to laboratory confirmed cases, and it was computationally efficient in doing so. The system was alsoable to detect a likely novel outbreak of the enterovirus D68 early in an outbreak that occurred in Allegheny County in 2014, as well as clinically characterize that outbreak disease accurately.
PubMed: 38805611
DOI: 10.2196/57349 -
BioRxiv : the Preprint Server For... May 2024Human metapneumovirus (HMPV) is a leading cause of respiratory infections in children, older adults, and those with underlying conditions . HMPV must evade immune...
UNLABELLED
Human metapneumovirus (HMPV) is a leading cause of respiratory infections in children, older adults, and those with underlying conditions . HMPV must evade immune defenses to replicate successfully; however, the viral proteins used to accomplish this are poorly characterized. The HMPV small hydrophobic (SH) protein has been reported to inhibit signaling through type I and type II interferon (IFN) receptors , in part by preventing STAT1 phosphorylation . HMPV infection also inhibits IL-6 signaling. However, the mechanisms by which SH inhibits signaling, and its involvement in IL-6 signaling inhibition are unknown. Here, we used transfection of SH expression plasmids and SH-deleted virus (ΔSH) to show that SH is the viral factor responsible for inhibition of IL-6 signaling during HMPV infection. Transfection of SH-expression vectors or infection with wildtype, but not ΔSH virus, blocked IL-6 mediated STAT3 activation. Further, JAK1 protein (but not RNA) was significantly reduced in cells infected with wildtype but not ΔSH virus. The SH-mediated reduction of JAK1 was partially restored by addition of proteasome inhibitors, suggesting proteasomal degradation of JAK1. Confocal microscopy indicated that infection relocalized JAK1 to viral replication factories. Co-immunoprecipitation showed that SH interacts with JAK1 and ubiquitin, further linking SH to proteasomal degradation machinery. These data indicate that SH inhibits IL-6 and IFN signaling in infected cells in part by promoting proteasomal degradation of JAK1 and that SH is necessary for IL-6 and IFN signaling inhibition in infection. These findings enhance our understanding of the immune evasion mechanisms of an important respiratory pathogen.
IMPORTANCE
Human metapneumovirus (HMPV) is a common cause of severe respiratory illness, especially in children and older adults, in whom it is a leading cause of hospitalization. Prior research suggests that severe HMPV infection is driven by a strong immune response to the virus, and especially by inflammatory immune signals like interferons (IFN). HMPV produces a small hydrophobic protein (SH) that is known to block IFN signaling, but the mechanism by which it functions, and its ability to inhibit other important immune signals remains unexplored. This paper demonstrates that SH can inhibit another related immune signal, IL-6, and demonstrates that SH depletes JAKs, critical proteins involved in both IL-6 and IFN signaling. A robust understanding of how HMPV and related viruses interfere with immune signals important for disease could pave the way for future treatments aimed at mitigating severe infections.
PubMed: 38798421
DOI: 10.1101/2024.05.10.593594 -
Viruses May 2024Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still...
Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation ( < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.
Topics: Humans; Coinfection; Respiratory Tract Infections; Italy; Child, Preschool; Child; Infant; Female; Male; Tertiary Care Centers; COVID-19; SARS-CoV-2; Hospitals, Pediatric; Adolescent; Human bocavirus; Virus Diseases; Hospitalization; Viruses; Infant, Newborn; Metapneumovirus
PubMed: 38793631
DOI: 10.3390/v16050750 -
Viruses Apr 2024Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the...
Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country.
Topics: Humans; Gabon; Genetic Variation; Phylogeny; COVID-19; Respiratory Tract Infections; SARS-CoV-2; Male; Adult; Female; Child; Middle Aged; Adolescent; Child, Preschool; Young Adult; Rhinovirus; Viruses; Metapneumovirus; Genome, Viral; Nasopharynx; Infant; Aged; Pandemics; Influenza A virus
PubMed: 38793579
DOI: 10.3390/v16050698 -
Microorganisms May 2024The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS),...
The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies.
PubMed: 38792840
DOI: 10.3390/microorganisms12051011 -
Journal of Korean Medical Science May 2024The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic.
METHODS
A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods.
RESULTS
A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic ( < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years ( = 0.003 and 0.007 for AdV and HCoV, respectively; < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023.
CONCLUSION
With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.
Topics: Humans; Child; COVID-19; Child, Preschool; Republic of Korea; Prospective Studies; Infant; Adolescent; Respiratory Tract Infections; SARS-CoV-2; Male; Female; Infant, Newborn; Pandemics
PubMed: 38769924
DOI: 10.3346/jkms.2024.39.e171 -
Infection and Drug Resistance 2024In addition to the well-known Whipple's disease (WD), Tropheryma Whipplei (TW) can also lead to acute pneumonia. There is no unified consensus on the susceptible...
BACKGROUND
In addition to the well-known Whipple's disease (WD), Tropheryma Whipplei (TW) can also lead to acute pneumonia. There is no unified consensus on the susceptible population, pathogenesis, clinical manifestations, diagnostic criteria, and treatment options for TW pneumonia.
CLINICAL PRESENTATION AND INTERVENTION
This is an elderly patient with multiple injuries caused by falling from a building, and was transferred to intensive care unit (ICU) for mechanical ventilation and empirical anti-infection treatment due to severe pneumonia, and then the results of targeted next-generation sequencing (tNGS) in patient's bronchoalveolar lavage fluid (BALF) suggested TW and human metapneumovirus (HMPV) infection, and after switching to anti-infective therapy for TW, the patient was successfully extubated and transferred out of the ICU.
CONCLUSION
This is the first case of using tNGS to diagnose severe pneumonia caused by TW and HMPV. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.
PubMed: 38745678
DOI: 10.2147/IDR.S451477 -
A Case Report of Sepsis-Induced Dilated Cardiomyopathy Secondary to Human Metapneumovirus Infection.Cureus Apr 2024Sepsis is a medical emergency that describes the body's systemic immunological response to an infectious process that can lead to end-stage organ dysfunction and death....
Sepsis is a medical emergency that describes the body's systemic immunological response to an infectious process that can lead to end-stage organ dysfunction and death. Sepsis-induced cardiomyopathy (SICM) is an increasingly recognized form of transient cardiac dysfunction characterized by left ventricular dilation, depressed ejection fraction, and recovery in 10 days without cardiac-related medical intervention. Injury to the myocardium by inflammatory cytokines has been proposed as one of the main causative mechanisms. Human metapneumovirus (hMPV) is a paramyxovirus and a common cause of respiratory tract infection that has been reported to modulate chemical mediators that produce inflammatory cytokines. Extra-pulmonary cardiac complications of hMPV have been reported; but literature on SICM associated with hMPV are very rare. We describe a case of a 43-year-old male with no known cardiac history diagnosed with SICM associated with hMPV. His sepsis was managed in the intensive care unit, and his heart ejection fraction improved within 10 days without the initiation of guideline-directed medical therapy.
PubMed: 38738071
DOI: 10.7759/cureus.57951 -
Scientific Reports May 2024Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory...
Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.
Topics: Animals; Pan troglodytes; Humans; Child; Female; Male; Child, Preschool; Common Cold; Adult; Uganda; Prospective Studies; Zoonoses; COVID-19; Ape Diseases; Respiratory Tract Infections; Rhinovirus; SARS-CoV-2; Incidence
PubMed: 38714841
DOI: 10.1038/s41598-024-61236-7 -
The New Microbiologica May 2024The COVID-19 pandemic forced the adoption of non-pharmaceutical interventions (NPIs) which influenced the circulation of other respiratory pathogens, such as Influenza...
The COVID-19 pandemic forced the adoption of non-pharmaceutical interventions (NPIs) which influenced the circulation of other respiratory pathogens, such as Influenza virus (FLU), Parainfluenza virus (PIV), Respiratory Syncytial virus (RSV), Rhinovirus (RV), Enterovirus (EV), Adenovirus (AdV), Human Metapneumovirus (hMPV), and Human Coronavirus (CoV). The aim of the current study was to investigate how, with the end of the pandemic, the withdrawal of the NPIs impacted on the circulation and distribution of common respiratory viruses. The analyzed samples were collected from June 2021 to March 2023 (post-pandemic period) and compared to ones from the pandemic period. Nucleic acid detection of all respiratory viruses was performed by multiplex real time Polymerase Chain Reaction (PCR) and sequencing was conducted by Next Generation Sequencing (NGS) technique. Our analysis shows that the NPIs adopted against SARS-CoV-2 were also effective in controlling the spread of other respiratory viruses. Moreover, we documented how RV/EVs were the most commonly identified species, with the more abundant strains represented by Coxsackievirus (CV)-A/B and RV-A/C. RV/EVs were also detected in some co-infection cases; in particular, the majority of co-infections concerned CV-B/RV-A, CV-B/ECHO. Given the pandemic potential of respiratory viruses, accurate molecular screening is essential for a proper surveillance and prevention strategy.
Topics: Humans; COVID-19; Italy; SARS-CoV-2; Respiratory Tract Infections; Pandemics; Viruses; Adult; Male; Child
PubMed: 38700887
DOI: No ID Found