Cause Of Respiratory Disease Research Articles

The Assessment of the Effectiveness of Ultrasound and Near-Infrared Spectroscopy of the Lungs for the Differential Diagnosis of Transient Tachypnea of Newborns and Congenital Pneumonia in Children over 350 Weeks of Gestation. The Prospective Study

Background. The most common cause of respiratory disorders (RD) in the first hours after birth in children older than 35 weeks of gestation are transient tachypnea of the newborns (TTN) and early neonatal infection, in particular, congenital pneumonia (CP). However, in the first 4 hours of life, there are no reliable methods for diagnosing these diseases. The aim of the study is to evaluate the effectiveness of ultrasound (US) and near-infrared spectroscopy (NIRS) of the lungs for the differential diagnosis of TTN and CP in children older than 35 weeks of gestation. Methods. A prospective single-center cohort study based on the Yekaterinburg Clinical Perinatal Center. Newborns older than 35 weeks of gestation with the development of RD in the first 4 hours of life were included, the sample size was 200 children. Upon admission to NICU, he performed studies: US and NIRS of the lungs on the lateral and posterior surfaces of the chest on both sides. A comparative analysis of the score of lung US and NIRS indicators in patients with TTN and CP was carried out. Results. During the study and subsequent analysis of the results, it was revealed that the studied methods for the differential diagnosis of TTN and CP have sensitivity and specificity, respectively: only US of the lungs 75.9% and 57.0%; only lung NIRS 77.6% and 74.6%; US and lung NIRS 86.2% and 84.5% together, the area under the curve 0.898, 95% CI 0.854–0.943, р < 0,001. There is also evidence that the pattern of consolidation in the lungs is significantly more often recorded by US at VP (р < 0,001). Conclusion. The study showed that the combined usage of US and lung NIRS has high sensitivity and specificity for the differential diagnosis of TTN and CP and is a promising method for early diagnosis of these diseases.

Prevalence and Genetic Diversity of Respiratory Syncytial Virus Reinfections in Young Thai Children, 2016-2023.

Although a vaccine for respiratory syncytial virus (RSV) is now available for pregnant women and the elderly, RSV remains a significant cause of respiratory illness in children globally. Reinfections by the same or different RSV subgroups in children residing in the tropics are currently under-studied. Therefore, we examined the patterns of RSV infection and reinfection in Thai children aged ≤ 5 years with respiratory symptoms from 2016 to 2023. Screening of 7710 pediatric respiratory specimens identified 1245 RSV-positive samples (16.1%), mostly from the rainy months (July-November). Interestingly, 74 children experienced two infections, and 6 had three infections. Reinfection by different RSV subgroups occurred in 30 children: 21 were initially infected with RSV-B and later with RSV-A, while 9 had the reverse pattern. Reinfections only by either RSV-A or RSV-B were observed in 22 and 2 children, respectively, with one child infected with RSV-A three times. All RSV-A reinfections belonged to the ON1 genotype, while RSV-B reinfections were BA9. Notably, reinfections across different seasons were observed within homologous pairs. These findings suggest a transitory immunity to natural RSV infection and provide the knowledge that may help optimize pediatric vaccination schedule. Ongoing epidemiological data on RSV are essential in monitoring genotype circulation and vaccine effectiveness.

Human parainfluenza virus 3 field strains undergo extracellular fusion protein cleavage to activate entry.

Enveloped viruses cause a wide range of diseases in humans. At the first step of infection, these viruses must fuse their envelope with a cell membrane to initiate infection. This fusion is mediated by viral proteins that require a critical activating cleavage event. It was previously thought that for parainfluenza virus 3, an important cause of respiratory disease and a representative of a group of important pathogens, this cleavage event was mediated by furin in the cell secretory pathways prior to formation of the virions. We show that this is only true for laboratory strain viruses, and that clinical viruses that infect humans utilize extracellular proteases that are only made by a small subset of cells. These results highlight the importance of studying authentic clinical viruses that infect human tissues for understanding natural infection.

Flexible and highly selective NO2 gas sensor based on direct-ink-writing of eco-friendly graphene oxide for smart wearable application

Nitrogen dioxide (NO2) is a major cause of respiratory disorders in outdoor and indoor environments. Real-time NO2 monitoring using nonintrusive wearable devices can save lives and provide valuable health data. This study reports a room-temperature, wearable, and flexible smart NO2 gas sensor fabricated via cost-effective printing technology on a polyimide substrate. The sensor uses alkali lignin with edge-oxidised graphene oxide (EGO-AL) ink, demonstrating a sensitivity of 1.70% ppm⁻1 and a detection limit of 12.70 ppb, with excellent selectivity towards NO2. The high sensing properties are attributed to labile oxygen functional groups from GO and alkali lignin, offering abundant interacting sites for NO2 adsorption and electron transfer. The sensor fully recovers to the baseline after heat treatment at 150 °C, indicating its reusability. Integration into lab coats showcased its wearable application, utilising a flexible printed circuit board to wirelessly alert the wearer via cell phone to harmful NO2 levels (>3 ppm) in the environment. This smart sensing application underscores the potential for practical, real-time air quality monitoring, personal safety enhancement, and health management.

Attenuation of PM2.5-Induced Lung Injury by 4-Phenylbutyric Acid: Maintenance of [Ca2+]i Stability between Endoplasmic Reticulum and Mitochondria.

Fine particulate matter (PM2.5) is a significant cause of respiratory diseases and associated cellular damage. The mechanisms behind this damage have not been fully explained. This study investigated two types of cellular damage (inflammation and pyroptosis) induced by PM2.5, focusing on their relationship with two organelles (the endoplasmic reticulum and mitochondria). Animal models have demonstrated that PM2.5 induces excessive endoplasmic reticulum stress (ER stress), which is a significant cause of lung damage in rats. This was confirmed by pretreatment with an ER stress inhibitor (4-Phenylbutyric acid, 4-PBA). We found that, in vitro, the intracellular Ca2+ ([Ca2+]i) dysregulation induced by PM2.5 in rat alveolar macrophages was associated with ER stress. Changes in mitochondria-associated membranes (MAMs) result in abnormal mitochondrial function. This further induced the massive expression of NLRP3 and GSDMD-N, which was detrimental to cell survival. In conclusion, our findings provide valuable insights into the relationship between [Ca2+]i dysregulation, mitochondrial damage, inflammation and pyroptosis under PM2.5-induced ER stress conditions. Their interactions ultimately have an impact on respiratory health.

Flow interruption compared to forced oscillatory maneuvers and esophageal balloon/pneumotachography for measurement of respiratory resistance in the horse.

Pulmonary function testing is critical to the diagnosis of equine asthma (EA), an important cause of respiratory disease in the horse, but its clinical use has remained elusive, unfortunately, due to the complexity of reference methods, esophageal balloon/pneumotachography (EBP), and forced oscillatory mechanics (FOM), so we sought a noninvasive, portable method for use in horses through rapid interruption of airflow for equilibration of alveolar pressure with proximal airway pressure, termed flow interruption (FI). Resistance (RINT) was computed as the relationship between the change in pressure at the nose before and immediately after interruption and flow immediately before interruption. A pilot study in five healthy university-owned animals using EBP and FI showed good correspondence between the two methods: RINT (0.33 ± 0.05 cmH2O/L/s) and RL (0.31 ± 0.06 cmH2O/L/s). In two separate populations of client-owned horses, with random assignment of methods to FI versus EBP (n = 8), RINT showed good correlation with RL in horses (rs = 0.995, P = 0.0002) and accords with RL, with no significant difference between RINT and RL. Using FOM (n = 12), RINT (0.67 ± 0.31 cmH2O/L/s) has good correlation with RRS measured with FOM (r = 0.834, P = 0.0001), but is consistently smaller than RRS (0.74 ± 0.33 cmH2O/L/s). Histamine bronchoprovocation (HBP) was performed in a subset of these horses: FI classified one horse in six as less reactive than did EBP, and FI classified one horse in seven as less reactive than did FOM.NEW & NOTEWORTHY We developed and document for the first time the use of flow interruption for the rapid and noninvasive measurement of resistance in equine patients and demonstrated short- and long-term stability and accuracy in comparison with the reference methods.

Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

Respiratory syncytial virus (RSV) is a major cause of respiratory illness and hospitalization in older adults during fall and winter in the United States. The 2023-2024 RSV season was the first during which RSV vaccination was recommended for U.S. adults aged ≥60 years, using shared clinical decision-making. On June 26, 2024, the Advisory Committee on Immunization Practices voted to update this recommendation as follows: a single dose of any Food and Drug Administration-approved RSV vaccine (Arexvy [GSK]; Abrysvo [Pfizer]; or mResvia [Moderna]) is now recommended for all adults aged ≥75 years and for adults aged 60-74 years who are at increased risk for severe RSV disease. Adults who have previously received RSV vaccine should not receive another dose. This report summarizes the evidence considered for these updated recommendations, including postlicensure data on vaccine effectiveness and safety, and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. These updated recommendations are intended to maximize RSV vaccination coverage among persons most likely to benefit, by clarifying who is at highest risk and by reducing implementation barriers associated with the previous shared clinical decision-making recommendation. Continued postlicensure monitoring will guide future recommendations.

Maternal Immunization Decision-Making Among Pregnant and Lactating People in Kenya: A Qualitative Exploration of Peer Influences on Vaccine Decision-Making for a Future RSV Vaccine

IntroductionRespiratory syncytial virus (RSV) is a leading cause of respiratory illness in infants globally, with new maternal RSV vaccines on the horizon. Vaccine decision-making during pregnancy is shaped by individual, interpersonal, community, and societal factors. This study explored key interpersonal influences on maternal vaccine decision-making among pregnant and lactating people (PLP) and community members in Kenya.MethodsThis qualitative study conducted in-depth interviews with six pregnant people, 18 lactating people, and 10 community members in one rural and one urban county in Kenya. Data were analyzed using a grounded theory approach.ResultsParticipants identified the pregnant person themself, male partners, other family members, peers, and healthcare providers (HCPs) as key influences on the maternal immunization decision-making process. The majority of interviewed PLP believed that decision-making during pregnancy should be left to themselves due to autonomy and their role as the primary caregiver. Community members, including male partners, also identified pregnant people as the key decision-maker. While some PLP said they deferred to male partners to make vaccine decisions, more felt that men were not as informed on maternal and child issues as themselves or other female peers and relatives. HCPs emerged as important influences and information sources for PLP during decision-making.DiscussionUnderstanding who influences vaccine-decision making during pregnancy will help inform demand generation strategies, and in turn, uptake of future maternal vaccines, including RSV vaccines. Given the strong role HCPs and peers have in the decision-making process, targeting key potential influences is essential to improve vaccine acceptance.

Evaluating Two Sampling Methods for Mycoplasma Bovis Diagnosis in American Bison (Bison bison).

Mycoplasma bovis is a bacterial pathogen endemic to cattle. In the early 2000s, M. bovis emerged as a cause of respiratory disease in American bison (Bison bison), causing significant morbidity and mortality. Bison herds that experience an outbreak of M. bovis are at higher risk for subsequent outbreaks, suggesting that chronic, subclinical infections can be established. Antemortem testing is therefore crucial to disease management; however, the precise sampling method to maximize detection of M. bovis in bison is unknown. We evaluated two sample types-superficial nasal swabs and deep nasopharyngeal swabs-collected from apparently healthy or symptomatic bison from January 2021 through December 2022. We used real-time PCR to detect M. bovis in 76/938 bison (8.1%) from 11 herds. For bison testing positive on at least one swab type, M. bovis was detected in 63/76 (82.8%) deep nasopharyngeal swabs and 29/73 (38.1%) superficial nasal swabs. Agreement between swabs for positive bison was 21% (n=16, kappa coefficient 0.319). We conclude that deep nasopharyngeal swabbing is more sensitive than superficial nasal swabbing for detection of M. bovis in bison and that low agreement between methods may be related to stage of infection. We further tested pooled samples by PCR and found that pooling of up to five samples can be effective to increase throughput and minimize costs. Management of wild bison relies on the ability to relocate animals to maintain gene flow and healthy populations. Sensitive and specific diagnostic tests are needed to inform decisions and minimize risk of transmission, especially from subclinical carriers. This study provides valuable insight that will inform best practices for M. bovis testing, thereby supporting the conservation of bison as healthy wildlife, which in turn promotes ecological restoration, safeguards cultural practices of Tribal Nations, and upholds the bison as a unique American icon.

Investigation of the epidemiology, pathogenicity and immunogenicity of Bordetella bronchiseptica isolated from cats and dogs in China from 2021 to 2023

Bordetella bronchiseptica (Bb) is recognized as a leading cause of respiratory diseases in dogs and cats. However, epidemiological data on Bb in dogs and cats in China are still limited, and there is no commercially available vaccine. Live vaccines containing Bb that are widely used abroad are generally effective but can establish latency and potentially reactivate to cause illness in some immunodeficient vaccinated recipients, raising safety concerns. In this study, 34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023. The PCR results showed that the percentage of positive Bb was 22.94% (441/1922), and more than 90% of the Bb isolates had four virulence factor-encoding genes (VFGs), namely, fhaB, prn, betA and dnt. All the isolated strains displayed a multidrug-resistant phenotype. The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice, and we found that eight isolates were highly virulent. Furthermore, the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice, and three Bb strains (WH1218, WH1203 and WH1224) with the best protective efficacy were selected. Dogs immunized with these three strains exhibited strong protection against challenge with the Bb field strain WH1218. Ultimately, the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate. Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb field strain WH1218. This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China, and all the isolates exhibited multidrug resistance. The present work contributes to the current understanding of the prevalence, antimicrobial resistance, and virulence genes of Bb in domestic dogs and cats. Additionally, our results suggest that the WH1218 strain is a promising candidate safe and efficacious inactivated Bb vaccine.

Mycoplasma ovipneumoniae in farmed whitetailed deer

Mycoplasma ovipneumoniae is an infectious cause of respiratory disease, previously assumed to cause disease only in members of the subfamily Caprinae (sheep, goats, muskox). This bacteri­um has sporadically been isolated from other species, including captive white-tailed deer (WTD); however, little is known about the incidence or significance of M. ovipneumoniae in this spe­cies. Chronic respiratory disease is a common problem in captive WTD, and due to the fastidious nature of M. ovipneumoniae, in­fections with this bacterium may be overlooked as a contributing factor. The objective of this study is to characterize the incidence of M. ovipneumoniae infection and its association with respira­tory disease in an intensively managed captive WTD herd. Ad­ditionally, future multi-locus and full genome sequence analyses will elucidate relatedness between M. ovipneumoniae isolates from WTD and other species.

Discovery of the tigecycline resistance gene cluster tmexCD3-toprJ1 in Pasteurella multocida strains isolated from pigs in China

Pasteurella multocida is a leading cause of respiratory disorders in pigs. However, the genotypes and antimicrobial resistance characteristics of P. multocida from pigs in China have not been reported frequently. In this study, we investigated 381 porcine strains of P. multocida collected in China between 2013 and 2022. These strains were assigned to capsular genotypes A (69.55%, n = 265), D (27.82%, n =106), and F (2.62%, n = 10); or lipopolysaccharide genotypes L1 (1.31%, n = 5), L3 (24.41%, n = 93), and L6 (74.28%, n = 283). Overall, P. multocida genotype A:L6 (46.46%) was the most-commonly identified type, followed by D:L6 (27.82%), A:L3 (21.78%), F:L3 (2.62%), and A:L1 (1.31%). Antimicrobial susceptibility testing showed that a relatively high proportion of strains were resistant to tetracycline (66.67%, n = 254), and florfenicol (35.17%, n = 134), while a small proportion of strains showed resistance phenotypes to enrofloxacin (10.76%, n = 41), ampicillin (8.40%, n = 32), tilmicosin (7.09%, n = 27), and ceftiofur (2.89%, n = 11). Notably, Illumina short-read and Nanopore long-read sequencing identified a chromosome-borne tigecycline-resistance gene cluster tmexCD3-toprJ1 in P. multocida. The structure of this cluster was highly similar to the respective structures found in several members of Proteus or Pseudomonas. It is assumed that the current study identified the tmexCD3-toprJ1 cluster for the first time in P. multocida.

Observations of Respiratory Syncytial Virus (RSV) Nucleic Acids in Wastewater Solids Across the United States in the 2022-2023 Season: Relationships with RSV Infection Positivity and Hospitalization Rates.

Respiratory syncytial virus (RSV) is a leading cause of respiratory illness and hospitalization, but clinical surveillance detects only a minority of cases. Wastewater surveillance could determine the onset and extent of RSV circulation in the absence of sensitive case detection, but to date, studies of RSV in wastewater are few. We measured RSV RNA concentrations in wastewater solids from 176 sites during the 2022-2023 RSV season and compared those to publicly available RSV infection positivity and hospitalization rates. Concentrations ranged from undetectable to 107 copies per gram. RSV RNA concentration aggregated at state and national levels correlated with infection positivity and hospitalization rates. RSV season onset was determined using both wastewater and clinical positivity rates using independent algorithms for 14 states where both data were available at the start of the RSV season. In 4 of 14 states, wastewater and clinical surveillance identified RSV season onset during the same week; in 3 states, wastewater onset preceded clinical onset, and in 7 states, wastewater onset occurred after clinical onset. Wastewater concentrations generally peaked in the same week as hospitalization rates but after case positivity rates peaked. Differences in onset and peaks in wastewater versus clinical data may reflect inherent differences in the surveillance approaches.

Bronchiolitis in an infant due to influenza A, necropsy findings: a case report

The influenza virus is an important cause of respiratory disease in infants and presents challenging differential diagnoses to investigate. This is a case report that involves a necroscopic study of a 2-month-old male infant, without previous comorbidities, with a serological diagnosis of influenza A and histopathological presentation of non-obliterating bronchiolitis. Infants are considered a high-risk group for flu complications due to the immaturity of the immune system and the ability to respond to respiratory infections. Furthermore, the severity of infection in infants may be worsened by the difficulty in quickly considering and treating the symptoms of the disease.

Epidemiology of influenza in Nigeria: A secondary analysis of the sentinel surveillance data in Nigeria from 2010 – 2020

BackgroundInfluenza is a leading cause of morbidity and mortality globally. Little is known of the true burden and epidemiology of influenza in Africa. Nigeria has a sentinel surveillance system for influenza virus (IFV). This study seeks to describe the epidemiological characteristics of influenza cases in Nigeria through secondary data analysis of the sentinel surveillance data from 2010 to 2020. MethodologyA retrospective secondary data analysis of data collected from patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) in the four Nigeria Influenza Sentinel Surveillance sites from January 2010 to December 2020. Data was cleaned and analyzed using Microsoft Excel and Epi info 7.2 for frequencies and proportions. The results of the analysis were summarized in tables and charts. ResultsA total of 13,828 suspected cases of influenza were recorded at the sentinel sites during the study period. About 10.3% (1421/13,828) of these tested positive for IFV of which 1243 (87.5%) were ILI patients, 175 (12.3%) SARI patients, and 3 (0.2%) novel H1N1 patients. Males accounted for 54.2% (770/1421) of the confirmed cases. The median age of confirmed cases was 3 years (range: <1month–97 years). Children 0–4 years accounted for 69.3% (985/1421) of all cases. The predominant subtypes were B lineage not determined (32.3%), A/H1N1 pdm09 (28.8%) and A/H3 (23.0%). There were periods of sustained transmission in most years with 2011 having the highest number of cases. Overall, there were more cases around January to March and August to November. Heart disease and chronic shortness of breath were the most common co-morbidities identified among confirmed cases. ConclusionInfluenza remains a significant cause of respiratory illness, especially among children aged less than 4 years. Influenza cases occur all year round with irregular seasonality in Nigeria. Children less than 4 years and those with co-morbidities should be prioritized for vaccination. Vaccine composition in the country should take cognizance of the prevailing strains which are type B (lineage not determined), A/H1N1 pdm09 and A/H3.

Epidemiology and Disease Burden of Respiratory Syncytial Virus Infection in Adults.

Respiratory syncytial virus (RSV) constitutes a significant cause of respiratory illness and mortality among older adults, a demographic that is expanding with considerable impact on healthcare systems worldwide. The actual burden of RSV in this population may still be underestimated, owing to factors such as low awareness and suboptimal diagnostic sensitivity in adults, the lack of robust RSV surveillance systems, and the infrequent use of diagnostic testing. Recent advancements in respiratory virus detection have spurred further exploration into appropriate preventive and therapeutic strategies. The recent approval of two vaccines highlights the critical need for the precise estimation of the RSV disease burden to optimize the effectiveness and cost-efficiency of immunization programs. This narrative review aimed to summarize the existing knowledge of the RSV burden in adults with a particular focus on older adults, incorporating data from Korea. Overall, current estimates indicate that the annual RSV attack rate in the general adult population ranges from 1 - 7%, increasing to approximately 4 - 10% among elderly and high-risk groups. The in-hospital mortality rate can be estimated to be around 7 - 10%, rising up to 40% among intensive care unit-admitted patients. To elucidate RSV's disease burden, further continuing research, including population-based studies, is necessary.

The Influence of Health Literacy and Self-Management on Emergency Healthcare Access for Rural Asthmatics: A Patient's Perspective.

Asthma is a leading cause of respiratory illness in Australia and has a significant prevalence in rural areas. Literature suggests living in rural areas can act as a barrier to receiving emergency healthcare for asthma exacerbations resulting in the need for further resources and advocacy in educating rural asthmatics about managing their condition and knowing when to access further help. This study aims to explore decision-making in accessing emergency healthcare for people with moderate to severe asthma exacerbations in rural New South Wales (NSW). A qualitative interpretative design involving semi-structured interviews with 12 participants was conducted between May and July 2021. Interviews were recorded and transcribed verbatim. Participants were asthmatics who had accessed emergency healthcare for a moderate to severe asthma exacerbation in NSW over the last five years. Data was thematically analysed and grouped into four overarching themes. Due to the depth and range of data this paper will be reporting on two of those themes. Past experiences as education and the impact of self-management strategies were both shown to be prominent influences that affected decisions on choosing to access emergency healthcare during a moderate to severe asthma exacerbation. Participants shared how their decision-making was shaped by health literacy gained from their past experiences of asthma exacerbations and dealing with emergency healthcare. In addition, self-management strategies were utilised to minimise the need to access emergency healthcare. This was achieved through telehealth appointments, lifestyle changes and non-pharmacological strategies. This study shows that an increase in health promotion activities throughout rural areas can help to reassure people about uncertainties that may be associated with their past experiences and improve health literacy. Additionally, providing tools to allow confident self-management of asthma effectively using evidence-based techniques to prevent it progressing to a moderate or severe exacerbation would also be of benefit.

A Serological Survey and Risk Factors of Respiratory Syncytial Virus in Goats in Different Locations in Al-Najaf, Iraq

Bovine respiratory syncytial virus (BRSV) is one of the most common causes of respiratory illness in goats globally, resulting in major financial losses. The goal of this Survey was to determine the incidence of Bovine Respiratory Syncytial virus in Al-Najaf goats and the risk factors for this disease. Between December 2021 and November 2022 For this study, 200 goats of various ages and breeds from Al Kufa, Qadisiyia, Hayderia, and Abbasyia in Al-Najaf, Iraq, were tested. The animals’ epidemiological information was recorded. An indirect Elisa test kit was used to establish the disease’s incidence. The incidence of BRSV in goats was 44.5%, and it was substantially higher in Goats aged more than one-year (50.4%). The incidence of BRSV in male and female goats did not vary significantly. Compared to samples taken during the other seasons, those collected in the winter had a significantly higher BRSV incidence. There was a significantly difference in disease infection rate (P≤0.05) among mixed goats compared with others that were not mixed with other specious. The results revealed that the imported animals had a significantly higher prevalence than the native goats. In Conclusion: Bovine Respiratory Syncytial Virus is predominant in goats from the Al-Najaf province and risk factors such as animal age, herd size, origin, and the herd’s geographical location are related to an increased occurrence of the disease in this region. Routine vaccination plans must be assumed to decrease the incidence of BRSV in goats.

1762. Clinical application of handheld ultrasound devices during the 2022 Sudan Virus disease Ebola outbreak in Uganda

Abstract Background The fluid status and causes of respiratory failure in patients with Ebola disease can be challenging to determine due to concomitant severe diarrhea, vascular leakage, and multiorgan failure. Point-of-care ultrasound (POCUS) could guide fluid resuscitation for patients in resource-limited settings. We present the clinical application of POCUS in the 2022 Sudan Virus disease Ebola outbreak in Uganda. Figure. Ultrasound findings from patient 2. 2A: Discrete B lines observed with an irregular pleural line; 2B: Inferior vena cava collapsibility &amp;lt;50% suggestive of adequate fluid resuscitation; 2C: parasternal short cardiac view with small pericardial effusion identified; 2D: apical cardiac view with small pericardial effusion redemonstrated. Methods A clinical research team in Fort Portal, Uganda was trained in advanced Infection Prevention and Control (IPC) to care for patients with Ebola disease and in POCUS for septic shock. The clinical team learned a standardized lung and cardiac critical care ultrasound approach to evaluate patients in septic shock. The scanning procedure was used during the care of 6 patients with confirmed Sudan virus disease within 2 weeks of outbreak declaration to make critical patient care decisions like fluid management. Chest X-ray services and mechanical ventilation were not accessible. A handheld Philips Lumify device was kept in the biocontainment area and was used in full personal protective equipment. Scanning procedures included 12-zone lung ultrasound and 4-view cardiac ultrasound scans to determine causes of respiratory disease and evaluate fluid status. Results Among 6 patients (age range 27 to 58 years; 1/6 female), 5/6 were in their third week of illness, and 1/6 was in his second week of illness. Lung ultrasound abnormalities included discrete B-lines (5/6 patients), confluent B-lines (1/6), irregular pleural lines (3/6 patients), and subpleural consolidations (1/6 patients). Two participants in respiratory distress had cardiac POCUS. Both had hyperdynamic left ventricular function and one had a small pericardial effusion (Figure). One patient had inferior vena cava (IVC) collapsibility &amp;lt; 50% (1.5 cm diameter), and another with a &amp;gt;50% IVC collapsibility (1.3 cm diameter). These findings contributed to a decision to continue fluid resuscitation. Conclusion Portable handheld ultrasound devices identified previously undescribed ultrasound features of Sudan virus disease. POCUS helped determine causes of respiratory failure and guided fluid resuscitation in a biocontainment ward without access to mechanical ventilation. Disclosures All Authors: No reported disclosures

Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus

Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.