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Frontiers in Immunology 2024Community-acquired pneumonia (CAP) is a global health concern, with 25% of cases attributed to (). Viral infections like influenza A virus (IAV), respiratory syncytial...
INTRODUCTION
Community-acquired pneumonia (CAP) is a global health concern, with 25% of cases attributed to (). Viral infections like influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) increase the risk of , leading to severe complications due to compromised host immunity.
METHODS
We evaluated the efficacy of an anti-PhtD monoclonal antibody (mAb) cocktail therapy (PhtD3 + 7) in improving survival rates in three viral/bacterial coinfection models: IAV/, hMPV/, and RSV/.
RESULTS
The PhtD3 + 7 mAb cocktail outperformed antiviral mAbs, resulting in prolonged survival. In the IAV/ model, it reduced bacterial titers in blood and lungs by 2-4 logs. In the hMPV/ model, PhtD3 + 7 provided greater protection than the hMPV-neutralizing mAb MPV467, significantly reducing bacterial titers. In the RSV/ model, PhtD3 + 7 offered slightly better protection than the antiviral mAb D25, uniquely decreasing bacterial titers in blood and lungs.
DISCUSSION
Given the threat of antibiotic resistance, our findings highlight the potential of anti-PhtD mAb therapy as an effective option for treating viral and secondary pneumococcal coinfections.
Topics: Animals; Humans; Antibodies, Monoclonal; Streptococcus pneumoniae; Mice; Superinfection; Coinfection; Respiratory Syncytial Virus Infections; Metapneumovirus; Influenza A virus; Disease Models, Animal; Pneumococcal Infections; Female; Mice, Inbred BALB C; Paramyxoviridae Infections; Antibodies, Viral
PubMed: 38933273
DOI: 10.3389/fimmu.2024.1364622 -
Animals : An Open Access Journal From... Jun 2024Avian metapneumovirus (aMPV) has been identified as an important cause of respiratory and reproductive disease, leading to significant productive losses worldwide....
Avian metapneumovirus (aMPV) has been identified as an important cause of respiratory and reproductive disease, leading to significant productive losses worldwide. Different subtypes have been found to circulate in different regions, with aMPV-A and B posing a significant burden especially in the Old World, and aMPV-C in North America, albeit with limited exceptions of marginal economic relevance. Recently, both aMPV-A and aMPV-B have been reported in the U.S.; however, the route of introduction has not been investigated. In the present study, the potential importation pathways have been studied through phylogenetic and phylodynamic analyses based on a broad collection of partial attachment (G) protein sequences collected worldwide. aMPV-B circulating in the U.S. seems the descendant of Eastern Asian strains, which, in turn, are related to European ones. A likely introduction pathway mediated by wild bird migration through the Beringian crucible, where the East Asian and Pacific American flight paths intersect, appears likely and was previously reported for avian influenza. aMPV-A, on the other hand, showed a Mexican origin, involving strains related to Asian ones. Given the low likelihood of trade or illegal importation, the role of wild birds appears probable also in this case, since the region is covered by different flight paths directed in a North-South direction through America. Since the information on the role of wild birds in aMPV epidemiology is still scarce and scattered, considering the significant practical implications for the poultry industry demonstrated by recent U.S. outbreaks, further surveys on wild birds are encouraged.
PubMed: 38929405
DOI: 10.3390/ani14121786 -
BMC Infectious Diseases Jun 2024Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease...
INTRODUCTION
Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).
METHODS
Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.
RESULTS
A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 10 genomic equivalents [GE/ml] vs. 3 × 10 GE/ml, p = 0.006) and MC (1 × 10 GE/ml vs. 1 × 10 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039).
CONCLUSION
Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.
TRIAL REGISTRATION
The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).
Topics: Humans; Case-Control Studies; Adolescent; Child; Male; Female; HIV Infections; Zimbabwe; Malawi; Lung Diseases; Young Adult; Chronic Disease; Bacteria; Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Respiratory System
PubMed: 38926682
DOI: 10.1186/s12879-024-09540-5 -
European Respiratory Review : An... Apr 2024Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune... (Review)
Review
Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus, , , , amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.
Topics: Humans; Animals; Neuroimmunomodulation; Respiratory System; Host-Pathogen Interactions; Respiratory Tract Diseases; Signal Transduction
PubMed: 38925790
DOI: 10.1183/16000617.0008-2024 -
Epidemiologia (Basel, Switzerland) May 2024Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic... (Review)
Review
Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic review with meta-analysis was designed to appraise all the available evidence on RSV infections among individuals in refugee camps. Three medical databases (PubMed, Embase, and Scopus) as well as the preprint repository medRxiv.org were searched for eligible observational studies, and the collected cases were pooled in a random-effects meta-analysis model. Heterogeneity was assessed using the I statistics. Funnel plots and a regression analysis were calculated for analyzing reporting bias. Eventually, six studies were retrieved from three areas (Bangladesh, Thailand, and Kenya), with pooled estimates of 129.704 cases per 1000 samples (95% CI 66.393 to 237.986) for RSV compared to 110.287 per 1000 people for influenza A (95% CI 73.186 to 162.889), 136.398 cases per 1000 people (95% CI 84.510 to 212.741) for human adenovirus (HAdV), 69.553 per 1000 people (95% CI 49.802 to 96.343) for parainfluenzavirus (PIFV), and 60.338 per 1000 people (95% CI 31.933 to 111.109) for human metapneumovirus (hMPV). Using influenza A as a reference group, the risk for a positive specimen was greater for RSV (relative risk [RR] 1.514, 95% CI 1.396 to 1.641) and HAdV (RR 1.984, 95% CI 1.834 to 2.146) and lower for influenza B (RR 0.276, 95% CI: 0.239 to 0.319), PIFV (RR: 0.889, 95% CI 0.806 to 0.981), and hMPV (RR 0.594, 95% CI 0.534 to 0.662). In summary, high rates of RSV infections were documented among individuals sheltered in refugee camps, stressing the importance of specifically designed preventive strategies.
PubMed: 38920751
DOI: 10.3390/epidemiologia5020016 -
NPJ Vaccines Jun 2024Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human...
Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.
PubMed: 38898106
DOI: 10.1038/s41541-024-00899-9 -
Cureus May 2024Introduction Viruses are the most common triggering factors for asthma exacerbation during the autumn and winter seasons. Viruses, such as influenza A and rhinovirus,...
Introduction Viruses are the most common triggering factors for asthma exacerbation during the autumn and winter seasons. Viruses, such as influenza A and rhinovirus, play a major role in the occurrence of severe exacerbation of asthma. This association between viral infection and asthma exacerbation in children is a result of the antiviral response of the immune system and various anti-inflammatory phenomena. In this work, we aimed to identify the virological profile of asthma exacerbation in children and analyze the correlation between viral infection type and the severity of exacerbation. Materials and methods This retrospective study was conducted from January 2016 to January 2024. The study included children hospitalized for asthma exacerbation associated with signs of viral-like respiratory infection with positive virological testing by multiplex real-time polymerase chain reaction or rapid test in the case of influenza A or respiratory syncytial virus (RSV). Data analysis was performed with Microsoft Excel and SPSS software using a previously established data collection sheet Results Thirty cases were collected for the study period. The mean age of the patients was 4 years and 8 months, with a male-to-female ratio of 3.3. Eighteen patients were known to have asthma, of which nine had uncontrolled asthma, and exacerbation was inaugural in 12 patients. Viral shedding was found in 14 patients. A viral agent was found in all patients, with coinfection of two or more viruses in three patients. The viruses found were influenza A (18 cases), coupled rhinovirus/enterovirus (eight cases), RSV (eight cases), human metapneumovirus (three patients), and parainfluenza type IV in only one inaugural patient. Asthma exacerbation was severe in 20 patients, moderate in eight patients, and two patients had severe acute asthma requiring intensive care management. We noted a higher frequency of severe exacerbation among those with an influenza A viral infection. All patients with RSV infection exhibited moderate exacerbation. No other significant correlation between asthma severity and other types of viruses was found. Conclusions Our results demonstrate the major role played by viruses in triggering asthma exacerbation, primarily influenza virus, followed by enterovirus, rhinovirus, RSV, and metapneumovirus. Larger-scale studies should be carried out to establish a more complete virological profile and further investigate the viral factor in the management of asthma in children.
PubMed: 38872674
DOI: 10.7759/cureus.60261 -
China CDC Weekly May 2024This study examines the seasonal and genetic characteristics of human metapneumovirus (HMPV) in Henan from 2017 to 2023.
INTRODUCTION
This study examines the seasonal and genetic characteristics of human metapneumovirus (HMPV) in Henan from 2017 to 2023.
METHODS
Samples from patients with acute respiratory infection (ARI) testing positive for HMPV were subjected to real-time reverse transcription polymerase chain reaction The G gene was amplified and sequenced from these samples for epidemiological and phylogenetic analysis.
RESULTS
We enrolled 2,707 ARI patients from October 2017 to March 2023, finding an HMPV positivity rate of 6.17% (167/2,707). Children under five exhibited the highest infection rate at 7.78% (138/1,774). The 2018 and 2019 HMPV outbreaks predominantly occurred in spring (March to May), with peak positivity rates of 31.11% in May 2018 and 19.57% in May 2019. A notable increase occurred in November 2020, when positivity reached a historic high of 42.11%, continuing until January 2021. From February 2021 through March 2023, no significant seasonal peaks were observed, with rates ranging from 0% to 8.70%. Out of 81 G gene sequences analyzed, 46.91% (38/81) were identified as subtype A (A2c: 45.67%, 37/81; A2b: 1.23%, 1/81) and 53.09% (43/81) as subtype B (B1: 9.88%, 8/81; B2: 43.21%, 35/81). Notably, an AAABBA switch pattern was observed in HMPV subtypes. The dominant strains were A2c in subtype A and B2 in subtype B.
CONCLUSIONS
Six years of surveillance in Henan Province has detailed the seasonal and genetic dynamics of HMPV, contributing valuable insights for the control and prevention of HMPV infections in China. These findings support the development of targeted HMPV vaccines and immunization strategies.
PubMed: 38846360
DOI: 10.46234/ccdcw2024.087 -
Frontiers in Bioengineering and... 2024Pandemics caused by respiratory viruses, such as the SARS-CoV-1/2, influenza virus, and respiratory syncytial virus, have resulted in serious consequences to humans and...
Pandemics caused by respiratory viruses, such as the SARS-CoV-1/2, influenza virus, and respiratory syncytial virus, have resulted in serious consequences to humans and a large number of deaths. The detection of such respiratory viruses in the early stages of infection can help control diseases by preventing the spread of viruses. However, the diversity of respiratory virus species and subtypes, their rapid antigenic mutations, and the limited viral release during the early stages of infection pose challenges to their detection. This work reports a multiplexed microfluidic immunoassay chip for simultaneous detection of eight respiratory viruses with noticeable infection population, namely, influenza A virus, influenza B virus, respiratory syncytial virus, SARS-CoV-2, human bocavirus, human metapneumovirus, adenovirus, and human parainfluenza viruses. The nanomaterial of the nanozyme (Au@Pt nanoparticles) was optimized to improve labeling efficiency and enhance the detection sensitivity significantly. Nanozyme-binding antibodies were used to detect viral proteins with a limit of detection of 0.1 pg/mL with the naked eye and a microplate reader within 40 min. Furthermore, specific antibodies were screened against the conserved proteins of each virus in the immunoassay, and the clinical sample detection showed high specificity without cross reactivity among the eight pathogens. In addition, the microfluidic chip immunoassay showed high accuracy, as compared with the RT-PCR assay for clinical sample detection, with 97.2%/94.3% positive/negative coincidence rates. This proposed approach thus provides a convenient, rapid, and sensitive method for simultaneous detection of eight respiratory viruses, which is meaningful for the early diagnosis of viral infections. Significantly, it can be widely used to detect pathogens and biomarkers by replacing only the antigen-specific antibodies.
PubMed: 38817925
DOI: 10.3389/fbioe.2024.1402831 -
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