Acute Respiratory Infections Research Articles

Prevalence of Child Fever, Acute Respiratory Infection, and Diarrhea and Their Risk Factors in Sierra Leone

Sierra Leone has the fourth-highest child mortality rate in Sub-Saharan Africa. This retrospective study aimed to estimate the nationwide prevalence of fever, acute respiratory infection (ARI), and diarrhea in children under 5 years in Sierra Leone, and to identify the risk factors associated with these diseases. We extracted patient information from the 2019 Sierra Leone Demographic and Health Survey data. Data were analyzed using multivariate logistic regression. In total, 8659, 8652, and 8650 children were included in the analyses of fever, ARI, and diarrhea, respectively. The analysis revealed that the nationwide prevalence rates of fever, ARI, and diarrhea were 16.8%, 14.2%, and 7.2%, respectively. Children aged 12–23 months were found to be the most susceptible. Compared to children consuming unimproved water, the highest prevalence rates of fever, ARI, and diarrhea were observed among children residing in households with tube wells or boreholes. The adjusted odds ratio for diarrhea prevalence among children drinking water from household tube wells or boreholes was 1.47 (95% confidence interval: 1.17–1.84, p < 0.001). This study has several limitations, including recall bias due to parental reporting. We suspect that the diseases may be associated with potential water contamination in tube wells or boreholes. We recommend national-level periodic inspections of water quality and community-level education on water supply management.

Microfluidic qPCR for detection of 21 common respiratory viruses in children with influenza-like illness.

Multiple respiratory viruses lead to high morbidity and mortality, yet global surveillance platforms focus primarily on seasonal influenza viruses. The COVID-19 pandemic and new RSV vaccines highlight the importance of a broader approach. Upper respiratory tract swabs from children aged 24-59months presenting with influenza-like illness in The Gambia were collected during follow-up of a live-attenuated influenza vaccine randomised controlled trial in 2017-18. A microfluidic quantitative polymerase chain reaction (qPCR) assay was established and used to detect 21 respiratory viruses. 76.6% of samples had one or more viruses detected (n = 121/158). The viruses detected most frequently were rhinovirus (n = 37/158, 23.4%) and adenovirus (n = 34/158, 21.5%), followed by parainfluenza virus 3, influenza B and human metapneumovirus B. A third of positive samples had multiple viruses detected (two n = 31/121, 25.6%; three n = 9/121, 7.4%). Our data demonstrates how microfluidic qPCR is a useful tool for high-throughput, comprehensive detection of multiple respiratory viruses in surveillance platforms. Rapidly changing epidemiology exemplifies the need for new, broader approaches to virus surveillance in low-resource settings to respond to future epidemics and to guide the need for and use of new prevention and therapeutic measures.

Update and narrative review of avian influenza (H5N1) infection in adult patients.

The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s. The most recent outbreaks in wild birds, domestic birds, and cows with some genetic variations and mutations among H5N1 strains has raised major concerns about potential transmission and public health risks. Symptoms range from asymptomatic to mild flu-like illness to severe illness that requires hospitalization. There are multiple vaccines in development for humans to protect against avian influenza, specifically the H5N1 virus. This includes a cell-based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz. Chemoprophylaxis against avian influenza following a suspected exposure should be started as soon as possible or no later than 48 h, and it is recommended to be continued for 7 days. The majority of avian influenza viruses are susceptible to neuraminidase inhibitors and cap-dependent endonuclease inhibitor. Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap-dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1.

Prediction of acute respiratory infections using machine learning techniques in Amhara Region, Ethiopia.

Many studies have shown that infectious diseases are responsible for the majority of deaths in children under five. Among these children, Acute Respiratory Infections is the most prevalent illness and cause of death worldwide. Acute respiratory infections continue to be the leading cause of death in developing countries, including Ethiopia. In order to predict the main factors contributing to acute respiratory infections in the Amhara regional state of Ethiopia, a machine learning technique was employed. This study utilized data from the 2016 Ethiopian Demographic and Health Survey. Seven machine learning models, including logistic regression, random forests, decision trees, Gradient Boosting, support vector machines, Naïve Bayes, and K-nearest neighbors, were employed to forecast the factors influencing acute respiratory infections. The accuracy of each model was assessed using receiver operating characteristic curves and various metrics. Among the seven models used, the Random Forest algorithm demonstrated the highest accuracy in predicting acute respiratory infections, with an accuracy rate of 90.35% and Area under the Curve of 94.80%. This was followed by the Decision Tree model with an accuracy rate of 88.69%, K-nearest neighbors with 86.35%, and Gradient Boosting with 82.69%. The Random Forest algorithm also exhibited positive and negative predictive values of 92.22% and 88.83%, respectively. Several factors were identified as significantly associated with ARI among children under five in the Amhara regional state, Ethiopia. These factors, included families with a poorer wealth status (log odds of 0.18) compared to their counterparts, families with four to six children (log odds of 0.1) compared to families with fewer than three living children, children without a history of diarrhea (log odds of -0.08), mothers who had occupation(log odds of 0.06) compared mothers who didn't have occupation, children under six months of age (log odds of -0.05) compared to children older than six months, mothers with no education (log odds of 0.04) compared to mothers with primary education or higher, rural residents (log odds of 0.03) compared to non-rural residents, families using wood as a cooking material (log odds of 0.03) compared to those using electricity. Through Shapley Additive exPlanations value analysis on the Random Forest algorithm, we have identified significant risk factors for acute respiratory infections among children in the Amhara regional state of Ethiopia. The study found that the family's wealth index, the number of children in the household, the mother's occupation, the mother's educational level, the type of residence, and the fuel type used for cooking were all associated with acute respiratory infections. Additionally, the research emphasized the importance of children being free from diarrhea and living in households with fewer children as essential factors for improving children's health outcomes in the Amhara regional state, Ethiopia.

Hardware treatment of diseases of the upper respiratory tract in acute respiratory viral infections

Acute respiratory viral infections are among the most common diseases affecting the health of the population and often leading to complications from the upper respiratory tract. Medical treatment of acute respiratory viral infection is often complemented by hardware therapies that help reduce the risk of complications and accelerate recovery. This paper describes modern hardware methods for the treatment of acute respiratory viral infections, including low-frequency ultrasound cavitation, photochromotherapy, ultraviolet irradiation and UHF therapy. The clinical efficacy was evaluated in comparison with drug-based approaches. The possibilities of using these methods both in medical institutions and at home using the MULTILOR device were also investigated. Data analysis has shown that the use of hardware treatment methods significantly reduces the severity of symptoms of acute respiratory viral infections, shortens the duration of the disease and reduces the risk of complications. It is important to note that devices such as MULTILOR allow for treatment at home, increasing the availability of therapy. Hardware treatment of acute respiratory viral infections (ARVI) of the upper respiratory tract is a promising direction in modern medical practice, due to its proven effectiveness, safety and variety of technologies used. The inclusion in therapeutic regimens of such methods as low-frequency ultrasonic cavitation, ultraviolet irradiation (UVF), as well as UHF therapy, allows not only to significantly accelerate the regression of clinical symptoms, but also prevents the development of complications often associated with acute respiratory viral infections. The combined effect of these methods contributes to a significant reduction in symptoms, improvement of the condition of the mucous membranes and prevention of disease recurrence.

ANALYSIS OF EARLY CHANGES IN OPTICAL COHERENCE TOMOGRAPHY AND OCULAR MANIFESTATIONS OF VOGT-KOYANAGI-HARADA DISEASE (CLINICAL CASES)

The difficulty of diagnosing Vogt-Koyanagi-Harada syndrome is due to the fact that in the prodromal stage, the inflammatory process develops in the vascular membrane without ocular manifestations, clinically, flu-like syndrome, meningism come out in the first place, mistakenly leading the patient to a doctor of another specialty.Objective: To analyze optical coherence tomography (OCT) data and clinical manifestations for early diagnosis and timely treatment of Vogt-Koyanagi-Harada syndrome.Methods: Data from two clinical cases are presented: patient T. with timely pathogenetic pulse therapy and patient B. with alternative treatment due to his refusal of the proposed therapy. Results: Against the background of treatment, both patients have an increase in visual acuity, but patient B. has a less favorable prognosis according to OCT data due to the lack of adequate therapy.Conclusion: OCT of the macular region makes it possible to make the correct diagnosis at an early date, which prevents the transition of the uveitic stage of Vogt-Koyanagi-Harada disease into a chronic one.

Estimates of resource use in the public-sector health-care system and the effect of strengthening health-care services in Malawi during 2015-19: a modelling study (Thanzi La Onse).

In all health-care systems, decisions need to be made regarding allocation of available resources. Evidence is needed for these decisions, especially in low-income countries. We aimed to estimate how health-care resources provided by the public sector were used in Malawi during 2015-19 and to estimate the effects of strengthening health-care services. For this modelling study, we used the Thanzi La Onse model, an individual-based simulation model. The scope of the model was health care provided by the public sector in Malawi during 2015-19. Health-care services were delivered during health-care system interaction (HSI) events, which we characterised as occurring at a particular facility level and requiring a particular number of appointments. We developed mechanistic models for the causes of death and disability that were estimated to account for approximately 81% of deaths and approximately 72% of disability-adjusted life-years (DALYs) in Malawi during 2015-19, according to the Global Burden of Disease (GBD) estimates; we computed DALYs incurred in the population as the sum of years of life lost and years lived with disability. The disease models could interact with one another and with the underlying properties of each person. Each person in the Thanzi La Onse model had specific properties (eg, sex, district of residence, wealth percentile, smoking status, and BMI, among others), for which we measured distribution and evolution over time using demographic and health survey data. We also estimated the effect of different types of health-care system improvement. We estimated that the public-sector health-care system in Malawi averted 41·2 million DALYs (95% UI 38·6-43·8) during 2015-19, approximately half of the 84·3 million DALYs (81·5-86·9) that the population would otherwise have incurred. DALYs averted were heavily skewed to children aged 0-4 years due to services averting DALYs that would be caused by acute lower respiratory tract infection, HIV or AIDS, malaria, or neonatal disorders. DALYs averted among adults were mostly attributed to HIV or AIDS and tuberculosis. Under a scenario whereby each appointment took the time expected and health-care workers did not work for longer than contracted, the health-care system in Malawi during 2015-19 would have averted only 19·1 million DALYs (95% UI 17·1-22·4), suggesting that approximately 21·3 million DALYS (20·0-23·6) of total effect were derived through overwork of health-care workers. If people becoming ill immediately accessed care, all referrals were successfully completed, diagnostic accuracy of health-care workers was as good as possible, and consumables (ie, medicines) were always available, 28·2% (95% UI 25·7-30·9) more DALYS (ie, 12·2 million DALYs [95% UI 10·9-13·8]) could be averted. The health-care system in Malawi provides substantial health gains with scarce resources. Strengthening interventions could potentially increase these gains, so should be a priority for investigation and investment. An individual-based simulation model of health-care service delivery is valuable for health-care system planning and strengthening. The Wellcome Trust, UK Research and Innovation, the UK Medical Research Council, and Community Jameel.

Burden and Risk Factors for Coinfections in Patients with a Viral Respiratory Tract Infection

Which patients should be monitored for coinfections or should receive empirical antibiotic treatment, in patients with an acute viral respiratory infection, is largely unknown. We evaluated the prevalence, characteristics, outcomes of coinfected patients, and risk factors associated with a coinfection among patients with an acute viral infection. A retrospective, single-center study recruited consecutive patients from October 2022 to March 2023 presenting to the emergency department with signs of a respiratory tract infection. Patients were screened for respiratory viruses and bacterial/fungal secondary infections according to local standard procedures. Outcomes included severe disease, in-hospital complications, all-cause in-hospital and ICU-related mortality, time to death, time to discharge, and time to coinfection. The analysis included 652 patients. A viral infection and a secondary bacterial/fungal infection were detected in 39.1% and 40% of cases. Compared with the rest of the cohort, coinfected patients had more frequently severe disease (88.3%, p < 0.001; 51% in patients with SARS-CoV-2) and higher in-hospital mortality (16.5%, p = 0.010). Nephropathy (OR 3.649, p = 0.007), absence of COVID-19 vaccination (OR 0.160, p < 0.001), SARS-CoV-2 infection (OR 2.390, p = 0.017), and lower blood pressure at admission (OR 0.980, p = 0.007) were independent risk factors for coinfection. Multidrug-resistant pathogens were detected in 30.8% of all coinfections. Patients with a viral infection are at high risk of bacterial coinfections, which carry a significant morbidity and mortality burden.

Immune Responses to Respiratory Syncytial Virus Vaccines: Advances and Challenges

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections.

A study of the correlation between meteorological factors and hospitalization for acute lower respiratory infections in children.

The study focuses on the effect of temperature and relative humidity on hospitalization for acute lower respiratory tract infections (LRTI) in children, respectively. In this study, the Distributed Lag Nonlinear Model (DLNM) based on quasi-Poisson distribution was used to investigate the effect of temperature and relative humidity on LRTI hospitalization in children, and subgroup analyses were conducted to identify sensitive populations by gender and age. A total of 43,951 children were hospitalized for LRTI from 1 January 2014 to 31 December 2019 in Lanzhou. The mean temperature during the study period was 11.34°C and the mean relative humidity was 51.03%. With reference to the median temperature of 12.7°C during the study period, both low (-4.1°C) and high (25.43°C) temperature had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-10 and lag0-9, respectively, with RR values of 1.645 (95%CI: 1.533, 1.764) and 1.098 (95%CI: 1.018, 1.184). With a reference to the median relative humidity of 51.17% during the study period, both low relative humidity (26.71%) and high relative humidity (76.70%, P95) had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-21 and lag21, respectively, with RR values of 1.235 (95% CI: 1.163, 1.311) and 1.044 (95% CI: 1.036, 1.051). The results of subgroup analyses showed that changes in meteorological factors had a stronger effect on Female and children aged 5-14years. The meteorological factors all have different degrees of influence on LRTI hospitalization in children. Girls and the children aged 5-14years are more sensitive. Attention to these meteorological risks can inform targeted interventions.

TRIM46 accelerates H1N1 influenza virus-induced ferroptosis and inflammatory response by regulating SLC7A11 ubiquitination.

Influenza A (H1N1) virus is an acute respiratory infection responsible for enormous morbidity and mortality worldwide. The tripartite motif-containing protein 46 (TRIM46) has an antiviral function that inhibits various viral infections. This study is designed to explore the role and mechanism of TRIM46 in the progress of H1N1 infection. Herein, we infected A549 or 16HBE cells with the H1N1 virus at different times to assess TRIM46 and solute carrier family 7 member 11 (SLC7A11) expression. TRIM46 and Influenza A nucleoprotein mRNA levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). TRIM46, solute carrier family 7 member 11 (SLC7A11), and Nucleoprotein protein levels were detected using protein level were detected by western blot assay. Cell virulence was determined using Virulence assay (TCID50) assay. Cell viability was determined using Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS), intracellular iron content, Malondialdehyde (MDA), and Glutathione (GSH) levels were determined using special assay kits. The stability of SLC7A11 was assessed by Cycloheximide (CHX) assay. Interaction between TRIM46 and SLC7A11 was verified using Co-immunoprecipitation (CoIP) assay. The biological role of TRIM46 was assessed in H1N1 virus-challenged lung injury mice in vivo. TRIM46 level was significantly increased during H1N1 virus infection, and SLC7A11 expression was decreased. TRIM46 downregulation could suppress H1N1 virus replication and relieve H1N1 infection-induced ferroptosis and inflammation in A549 or 16HBE cells. Mechanistically, TRIM46 could promote SLC7A11 ubiquitination and decrease its stability. TRIM46 knockdown repressed H1N1 virus-induced lung injury in vivo. TRIM46 could contribute to influenza A H1N1 virus infection by promoting SLC7A11 ubiquitination in A549 cells, which indicates that targeting TRIM46 may improve the prognosis of patients.

Air Purifiers and Acute Respiratory Infections in Residential Aged Care: A Randomized Clinical Trial.

The effectiveness of in-room air purification for the reduction of acute respiratory infections (ARIs) in residential aged-care facilities (RACFs) is unknown. To investigate the effectiveness of in-room air purifiers with high-efficiency particulate air (HEPA)-14 filters in reducing the incidence of ARIs among residents of RACFs. This randomized clinical trial used a multicenter, double-blind, 2-period, 2-treatment crossover design for 6 months from April 7 to October 26, 2023, in 3 RACFs with a bed capacity of 50 to 100 in New South Wales, Australia. The purposive sampling approach included permanent residents in private rooms in the enrolled RACFs. Data collection was performed every 2 weeks and required no additional follow-up beyond the final data collection on October 31, 2023. An air purifier containing a HEPA-14 filter was placed in rooms of participants in the intervention group, and an air purifier without a HEPA-14 filter was placed in rooms of the control participants. The groups crossed over after 3 months. The primary outcome was the incidence of ARIs, assessed with logistic mixed-model regression. Among 135 participants randomized (70 to the intervention-first group and 65 to the control-first group), 78 (57.8%) were female; mean (SD) age was 85.2 (8.6) years. In the intention-to-treat analysis, the use of air purifiers with HEPA-14 filters did not reduce ARIs compared with the control (OR, 0.57; 95% CI, 0.32-1.04; P = .07). Among the 104 participants who completed the entire study, the intervention reduced ARI incidence from 35.6% (37 participants) in the control group to 24.0% (25 participants) in the intervention group (OR, 0.53; 95% CI, 0.28-1.00; P = .048). In this clinical trial investigating use of air purifiers with HEPA-14 filters for reducing ARIs, no significant between-group difference was found in the intention-to-treat analysis. However, a significant reduction in ARIs was identified among participants who completed the entire study. These findings may help inform future large-scale studies of respiratory infectious diseases. ANZCTR identification: ACTRN12623000347662.

Spatial and temporal transmission dynamics of respiratory syncytial virus in New Zealand before and after the COVID-19 pandemic.

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015-2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

Real-world use of multiplex point-of-care molecular testing or laboratory-based molecular testing for influenza-like illness in a 2021 to 2022 US outpatient sample.

While molecular testing is recommended for symptomatic patients suspected of having coronavirus disease 2019 (COVID-19), limited data are available examining real-world use of tests for severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the impact of SARS-CoV-2 testing on patient outcomes. In this retrospective cohort study using de-identified administrative claims data in the Optum Labs Data Warehouse, we identified 2 groups of patients with ≥1 outpatient claims with a procedure code for SARS-CoV-2 testing between January 2021 and September 2022. Group 1 had ≥1 claims with CPT code 0240U or 0241U ("Xpert Xpress") (N = 51,602); Group 2 had ≥1 claims for laboratory-based molecular testing (N = 317,192). Outcomes assessed on the identification date and through the 90-day follow-up included claims evidence of use of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) tests, diagnosis of active COVID-19, influenza, or RSV, and use of treatments (antivirals for COVID-19, influenza, and RSV and other treatments for COVID-19 and RSV). Patients in Group 1 had fewer tests for SARS-CoV-2, influenza, or RSV (mean ± standard deviation 1.6±1.4 versus 2.6±2.6, standardized difference -0.45), faster time to diagnosis of COVID-19 (median 0 versus 4 days, standardized difference -0.27) or influenza (median 0 versus 5 days, standardized difference -0.74), and faster time to treatment of COVID-19, influenza, or RSV (median 1 versus 5 days, standardized difference 0.16) than patients in Group 2. In this nationwide real-world study of outpatient testing, use of point-of-care molecular multiplex SARS-CoV-2 testing resulted in fewer claims for SARS-CoV-2, influenza, and RSV tests, faster time to diagnosis, and faster time to treatment than laboratory-based molecular testing.

CTIM-10. PHASE 1 TRIAL OF PERSONALIZED NEOANTIGEN VACCINES IN COMBINATION WITH STANDARD CARE TO TREAT GLIOBLASTOMA

Abstract The tumor microenvironment (TME) of glioblastoma (GBM) is populated by cells that foster immunosuppression. Reversing immunosuppression and promoting tumor surveillance by T cells that recognize the antigens generated by tumor-specific mutations (neoantigens) is critical to eliminating the tumor cells. In a phase 1 clinical trial of newly diagnosed GBM (NCT03223103), patients were treated with personalized neoantigen vaccines (PNV) combined with standard of care (resection, radiotherapy, temozolomide chemotherapy, and TTFields). The neoantigens were identified using the OpenVax computational pipeline. Primary endpoints included safety and feasibility, and the secondary endpoints included PFS, OS, TME analysis, and immunogenicity assays. The study enrolled 12 patients, ages 32-84, between December 2017 - July 2020. With a feasibility endpoint of one successful PNV administration, all patients got at least 6. All developed PNV-related injection site reactions, and flu-like symptoms grade 1-2. Concomitant use with TTFields did not increase toxicity. None of the patients exhibited dose-limiting toxicity within 30 days of receiving the PNV. However, one developed grade 3 SAE, consisting of seizures, neck pain, and progressive neurological deficits, after vaccine 10, culminating in a grade 5 SAE and brain demyelination 10 months later. Assays performed on this subject showed induction of neoantigen-specific responses with PNV. PNV induced CD4+ and CD8+ T cells reactive against multiple vaccine peptide sequences with CD8+ T cell cross-reactivity against one wild-type epitope. Other patients had immunogenicity against the vaccinated peptides. Overall, the 6 months PFS was 100%, with 67% 2-year and 58% 3-year survival. Although the mutation burden is low in GBM, neoantigens were detected in all tumors, and PNV were manufactured for all patients. PNV with synthetic long peptides combined with standard care treatment may help improve outcomes in GBM. Cross-reactivity may potentially be responsible for post-vaccination T-cell demyelination. Further evidence is needed to substantiate a direct effect. Funding: CRI - V Foundation CLIP (#3680)

Venous intestinal ischemia of fungal origin as a cause of intestinal obstruction in immunocompromised patients: case report and literature review

BackgroundMucormycosis is a highly lethal opportunistic fungal disease caused by ubiquitous molds of the order Mucorales, with Rhizopus, Lichtheimia and Mucor being the most common genera. This rare disease primarily affects immunocompromised patients, with presentations ranging from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion, leading to thrombosis and tissue infarction. Gastrointestinal mucormycosis is the least common clinical presentation and is believed to be secondary to spore ingestion. It can involve multiple components of the gastrointestinal tract, such as the stomach, liver, ileum, and colon, with nonspecific manifestations, including pain, nausea, vomiting, and abdominal distension. The initial clinical presentation may even manifest as gastrointestinal bleeding due to gastric ulceration or intestinal perforation.Case presentationHere we present the case of a 48-year-old male patient with a 9-year history of human immunodeficiency virus (HIV) infection who was hospitalized in the context of febrile neutropenia and whose acute respiratory infection was documented; therefore, antibiotic treatment was initiated. However, due to persistent febrile peaks and peripheral blood showing documentation of multilineage cytopenias, a bone marrow biopsy was performed, compatible with presenting features of marrow myelodysplasia. During hospitalization, the patient presented left flank abdominal pain, and an abdominal computed tomography (CT) scan revealed signs of intussusception of a small bowel loop at the distal jejunum level, leading to intestinal obstruction with ischemic progression, requiring ileectomy (60 cm). Histopathological analysis of the resected intestine revealed severe transmural ischemic changes associated with venous thrombosis due to fungal structures, with histochemical studies demonstrating the presence of zygomycete (Mucor) fungal structures, leading to the initiation of treatment with amphotericin B. However, despite treatment, the patient experienced progressive clinical deterioration with persistent fever and ventilatory failure, with follow-up tests showing absolute neutropenia and blood cultures positive for yeast, leading to death 52 days after admission.ConclusionsThe diagnosis of intestinal mucormycosis may be delayed due to the lack of specificity of the signs and symptoms. Pathologists as well as histopathological studies are essential for timely treatment.

Clinical relevance of lung microbiota composition in critically ill children with acute lower respiratory tract infections: insights from a retrospective analysis of metagenomic sequencing.

Acute lower respiratory tract infections (ALRIs) is a leading cause of child mortality worldwide. Metagenomic next-generation sequencing (mNGS) identifies ALRIs pathogens and explores the lung microbiota's role in disease severity and clinical outcomes. This study examines the association between lung microbiota and ALRIs outcomes in children, exploring its potential as a prognostic biomarker. We retrospectively analyzed mNGS data from the bronchoalveolar lavage fluid (BALF) of 83 pediatric ALRIs patients from 2019 to 2023. Microbial diversity and relative abundances of specific taxa were compared between survivor and non-survivor groups, as well as between varying severity levels. LEfSe was employed to identify key biomarkers related to survival and disease severity. Among the 83 patients, 68 survived and 15 died. Patients were also divided into a low severity group (n = 38) and a moderate-to-very-high severity group (n = 45) according to mPIRO score at admission. Significant differences in beta diversity were observed between the survival groups and across different severity levels. Prevotella, Haemophilus and Veillonella exhibited higher abundances in both the survivor and low severity groups, suggesting their potential as predictors of better outcomes. Conversely, Enterococcus and Acinetobacter baumannii were more prevalent in the non-survivor and moderate-to-very-high severity groups. Additionally, Streptococcus pneumoniae and Streptococcus mitis showed increased abundances in survivors. LEfSe further revealed that these microorganisms may predict outcomes and severity in ALRIs. Our findings underscore the complex relationship between lung microbiota and ALRIs, with specific microbial profiles associated with disease severity and clinical outcomes. This underscores the need for further research to explore and validate its prognostic predictive capacity. Not applicable.

Hospital-based cross-sectional study on the clinical characteristics of children with severe acute respiratory infections in Hungary

BackgroundSevere acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV.MethodsWe collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed.ResultsOur results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4–7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43–7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14–6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29–8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35–4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days.ConclusionsOur research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics.

Factors associated with outcome in a national cohort of rhinovirus hospitalized patients in Brazil in 2022

The common cold is the primary cause of illness in the community, with over 200 viral strains identified, and rhinovirus infections being the most prevalent. Coronavirus Disease 19 (COVID-19) is also a significant cause of severe illness. The burden of acute respiratory infections has a significant impact on the economy, resulting in absenteeism from work and school. Rhinovirus infections can exacerbate asthma and other chronic diseases, leading to hospitalization. The objective of this study is to investigate the factors associated with death and survival in patients hospitalized for rhinovirus in Brazil in 2022. This is a retrospective cohort study using data from the national surveillance of Severe Acute Respiratory Syndrome (SARS) in 2022 in Brazil, with all the norrifications. We analysed and compared clinical and epidemiological factors and outcomes between survivors and deaths in patients hospitalised for rhinovirus. The absolute and relative frequencies were calculated according to the states. Bivariate analysis was performed using chi-squared test and Fisher’s exact test, while multivariate analysis was performed using COX regression. Out of 8,130 cases of SARS caused by rhinovirus, 291 (3.58%) resulted in death while 7839 (96.47%) patients survived. The factors associated with death were invasive ventilation (p- < 0.001 HR 4.888 CI 95% 3.816–6.262), bocavirus (p- < 0.001 HR 4.204 CI 95% 2.595–6.812), immunodepression/Immunosuppression (p- < 0.001 HR 2.417 CI 95% 1. 544–3, 786), COVID-19 (p- < 0.001 HR 2.167 CI 95% 1.495–3.142), chronic neurological diseases (p-0.007 HR 1.610 CI 95% 1.137–2.280), abdominal pain (p-0.005 HR 1.734 CI 95% 1.186–2.537), age (p- < 0.001 HR 1.038 CI 95% 1.034–1.042). The survival factors identified in this study were dyspnea (p = 0.005; HR 0.683; CI 95% 0.524–0.889), cough (p < 0.001; HR 0.603; CI 95% 0.472–0.769), and asthma (p = 0.052; HR 0.583; CI 95% 0.339–1.004). Additionally, the study found that receiving a COVID-19 booster dose was also a significant survival factor (p = 0.001; HR 0.570; CI 95% 0.415–0.784). The factors associated with death were similar to those in the literature, and the factors associated with survival were also similar, except for the booster dose of the COVID-19 vaccine, which we didn’t find in any studies. Our study is the first to associate the full course of the COVID-19 vaccine with survival in those hospitalized for rhinovirus, regardless of COVID-19 and rhinovirus co-detection.

Respiratory viruses associated with severe acute respiratory infection in children aged

With the increased availability of licensed vaccines for respiratory viruses such as severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus (RSV), and influenza virus, a better understanding of the viral aetiology of severe acute respiratory infections (SARI) among children could help in optimising the use of these vaccines. We conducted a study among children aged <5 years hospitalised with SARI at a tertiary care children's hospital in north India and tested for common respiratory pathogens. We randomly enrolled eligible SARI cases aged <5 years from August 2013 to July 2015. SARI cases were defined as either <7-day history of fever with cough or in children aged eight days to three months, a physician diagnosis of acute lower respiratory infection requiring hospitalisation. We also enrolled an age-group matched control without any acute illness in a 2:1 ratio from the outpatient clinic within 24 hours of case enrolment. Nasopharyngeal and/or oropharyngeal swabs were collected and tested using TaqMan Array Cards, a real-time reverse transcription polymerase chain reaction-based multi-pathogen testing platform for selected respiratory viruses among the enrolled cases and controls. We compared the prevalence of each pathogen among cases and controls using the χ2 (χ2) or Fisher exact test (P < 0.05). We used logistic regression to estimate adjusted odds ratios (aORs) which were then used to calculate aetiologic fractions (EFs). We enrolled 840 cases and 419 outpatient controls. Almost half of the individuals in the whole sample were aged <6 months (n = 521, 41.4%). Females made up 33.7% of cases and 37.2% of controls. Viral detections were more common among cases (69%, 95% confidence interval (CI) = 66, 73) compared to controls (33%; 95% CI = 29, 38) (P < 0.01). RSV (n = 257, 31%; 95% CI = 28, 34%) was the most common virus detected among cases. Influenza A was detected among 24 (3%; 95% CI = 2, 4%), and influenza B among 5 (1%; 95% CI = 0, 1%) cases. The association between the virus and SARI was strongest for RSV (aOR = 23; 95% CI = 12, 47; EF = 96%). Antivirals were administered to 1% of SARI cases while 78% received antibiotics. Using a multi-pathogen molecular detection method, we detected respiratory viruses among more than two-thirds of children aged <5 years admitted with SARI in the Delhi tertiary care children's hospital. The guidelines for preventing and managing SARI cases among children could be optimised further with the improved availability of antivirals and vaccines.