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BMC Infectious Diseases May 2024Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the...
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control.
METHODS
We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection.
RESULTS
The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants.
CONCLUSIONS
The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.
Topics: Humans; Respiratory Syncytial Virus Infections; Hospitalization; Infant; Infant, Premature; Infant, Newborn; Western Australia; Female; Respiratory Syncytial Virus, Human; Age Factors; Male; Risk Assessment; Risk Factors
PubMed: 38773455
DOI: 10.1186/s12879-024-09400-2 -
Nature Communications May 2024The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the...
The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop β1S2-β1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.
Topics: Animals; Antibodies, Neutralizing; Female; Antibodies, Viral; Henipavirus Infections; Cryoelectron Microscopy; Viral Fusion Proteins; Humans; Viral Envelope Proteins; Nipah Virus; Virus Internalization; Henipavirus; Cricetinae; Cross Reactions; Hendra Virus; Macaca; Mesocricetus; Crystallography, X-Ray
PubMed: 38773072
DOI: 10.1038/s41467-024-48601-w -
Antiviral Research Jul 2024Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic...
Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.
Topics: Antiviral Agents; Respiratory Syncytial Virus Infections; Animals; Humans; Virus Replication; Respiratory Syncytial Virus, Human; Sheep; Drug Resistance, Viral; Viral Proteins; Lung
PubMed: 38772503
DOI: 10.1016/j.antiviral.2024.105907 -
Human Genomics May 2024After the occurrence of the COVID-19 pandemic, detection of other disseminated respiratory viruses using highly sensitive molecular methods was declared essential for...
BACKGROUND
After the occurrence of the COVID-19 pandemic, detection of other disseminated respiratory viruses using highly sensitive molecular methods was declared essential for monitoring the spread of health-threatening viruses in communities. The development of multiplex molecular assays are essential for the simultaneous detection of such viruses even at low concentrations. In the present study, a highly sensitive and specific multiplex one-step droplet digital PCR (RT-ddPCR) assay was developed for the simultaneous detection and absolute quantification of influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), and beta-2-microglobulin transcript as an endogenous internal control (IC B2M).
RESULTS
The assay was first evaluated for analytical sensitivity and specificity, linearity, reproducibility, and recovery rates with excellent performance characteristics and then applied to 37 wastewater samples previously evaluated with commercially available and in-house quantitative real-time reverse transcription PCR (RT-qPCR) assays. IAV was detected in 16/37 (43%), IBV in 19/37 (51%), and RSV in 10/37 (27%) of the wastewater samples. Direct comparison of the developed assay with real-time RT-qPCR assays showed statistically significant high agreement in the detection of IAV (kappa Cohen's correlation coefficient: 0.834, p = 0.001) and RSV (kappa: 0.773, p = 0.001) viruses between the two assays, while the results for the detection of IBV (kappa: 0.355, p = 0.27) showed good agreement without statistical significance.
CONCLUSIONS
Overall, the developed one-step multiplex ddPCR assay is cost-effective, highly sensitive and specific, and can simultaneously detect three common respiratory viruses in the complex matrix of wastewater samples even at low concentrations. Due to its high sensitivity and resistance to PCR inhibitors, the developed assay could be further used as an early warning system for wastewater monitoring.
Topics: Wastewater; Influenza A virus; Humans; Influenza B virus; Multiplex Polymerase Chain Reaction; Sensitivity and Specificity; Respiratory Syncytial Viruses; Reproducibility of Results; Influenza, Human; Respiratory Syncytial Virus, Human; Real-Time Polymerase Chain Reaction; SARS-CoV-2
PubMed: 38769549
DOI: 10.1186/s40246-024-00614-8 -
Nature Communications May 2024The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented...
The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L-P complex conformations from the mumps virus (MuV), a typical member of nsNSVs, via cryogenic-electron microscopy. One conformation presents all five domains of L forming a continuous RNA tunnel to the methyltransferase domain (MTase), preferably as a transcription state. The other conformation has the appendage averaged out, which is inaccessible to MTase. In both conformations, parallel P tetramers are revealed around MuV L, which, together with structures of other nsNSVs, demonstrates the diverse origins of the L-binding X domain of P. Our study links varying structures of nsNSV polymerase complexes with genome replication and transcription and points to a sliding model for polymerase complexes to advance along the RNA templates.
Topics: Cryoelectron Microscopy; Mumps virus; Viral Proteins; Models, Molecular; RNA, Viral; DNA-Directed RNA Polymerases; Protein Domains; Phosphoproteins; RNA-Dependent RNA Polymerase; Virus Replication; Transcription, Genetic; Protein Conformation
PubMed: 38760379
DOI: 10.1038/s41467-024-48389-9 -
The Journal of Infection Jul 2024Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also...
BACKGROUND
Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection.
METHODS
This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48 h.
RESULTS
One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one-month mortality were age and maximum oxygen flow during hospitalization.
CONCLUSION
RSV-associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate.
Topics: Humans; Respiratory Syncytial Virus Infections; Tertiary Care Centers; Female; Male; Retrospective Studies; Aged; France; Aged, 80 and over; Respiratory Syncytial Virus, Human; Immunocompetence; Respiratory Insufficiency; Hospitalization
PubMed: 38759759
DOI: 10.1016/j.jinf.2024.106180 -
Veterinaria Italiana Mar 2024This study was conducted to estimate the seroprevalence of Peste des petits ruminants virus (PPRV) and to determine the virus distribution in unvaccinated goats in the...
This study was conducted to estimate the seroprevalence of Peste des petits ruminants virus (PPRV) and to determine the virus distribution in unvaccinated goats in the Pantnagar region of Uttarakhand state, India. A total of 212 serum samples from goats were collected randomly from various villages in three districts (Udhamsingh Nagar, Nainital, and Almora) of Uttarakhand. Serum samples were tested for anti-PPRV antibodies by a commercially available kit. RNA was extracted from the clinical samples and it was subjected to one-step RT-PCR, followed by virus isolation from positive samples. A total of 41 animals from various villages were found to be seropositive with a prevalence rate of 19.33%. PPR outbreaks were also reported from the Tarai region of Uttarakhand, and detection by PCR confirmed PPRV in 8 goats. Two representative swab samples were subjected to virus isolation in Vero cells and both samples showed typical cytopathic effects. The present study shows that PPRV is circulating in the Tarai region of Uttarakhand and mass vaccination for PPR must be followed in this region to increase herd immunity to a protective level. To the best of our knowledge, this is the first investigation of PPRV seroprevalence in unvaccinated goats of Uttarakhand, India.
Topics: Animals; Peste-des-Petits-Ruminants; India; Peste-des-petits-ruminants virus; Goats; Goat Diseases; Seroepidemiologic Studies
PubMed: 38757513
DOI: 10.12834/VetIt.2988.21721.3 -
Euro Surveillance : Bulletin Europeen... May 2024
Letter to the editor: Atypical age distribution and high disease severity in children with RSV infections during two irregular epidemic seasons throughout the COVID-19 pandemic.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; SARS-CoV-2; Child, Preschool; Infant; Child; Severity of Illness Index; Age Distribution; Seasons; Male; Female; Pandemics; Respiratory Syncytial Virus, Human; Adolescent
PubMed: 38757287
DOI: 10.2807/1560-7917.ES.2024.29.20.2400269 -
Influenza and Other Respiratory Viruses May 2024Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015...
BACKGROUND
Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021.
METHODS
This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray.
RESULTS
Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases.
CONCLUSION
In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.
Topics: Humans; Mongolia; Respiratory Syncytial Virus Infections; Infant; Influenza, Human; Female; Male; Respiratory Syncytial Virus, Human; Child, Preschool; Nasopharynx; Infant, Newborn; Incidence; Hospitalization; Streptococcus pneumoniae; Respiratory Tract Infections
PubMed: 38757258
DOI: 10.1111/irv.13303 -
Indian Journal of Medical Ethics 2024As the world grapples with the constant threat of new pathogens, the role of government oversight in research and response efforts has become a topic of considerable...
As the world grapples with the constant threat of new pathogens, the role of government oversight in research and response efforts has become a topic of considerable debate in the academic community. In the recently released "SOP [standard operating procedure] for Nipah virus research in Kerala for studies involving human participants / human samples" by the Government of Kerala, the SOP, apart from administrative permission, requires the proposal to be cleared by the Institutional Research Committee at a Government Medical College, and the inclusion of an investigator from a government institution [1]. In these challenging times, it is crucial to weigh the pros and cons of stringent administrative controls to ensure an effective and ethical approach to tackling emerging infectious diseases.
Topics: Humans; Communicable Diseases, Emerging; India; Biomedical Research; Government Regulation; Nipah Virus; Henipavirus Infections; Ethics Committees, Research
PubMed: 38755764
DOI: 10.20529/IJME.2024.016