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JAMA Jun 2024
Topics: Animals; Cattle; Female; Humans; Cattle Diseases; Dairying; Disease Outbreaks; Influenza in Birds; Influenza, Human; Public Health; United States; Oseltamivir; Antiviral Agents; Red Meat; Milk; Food Supply; Food Quality; Influenza A Virus, H5N1 Subtype; Food Industry
PubMed: 38718040
DOI: 10.1001/jama.2024.8886 -
Influenza and Other Respiratory Viruses May 2024The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household.
METHODS
A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV.
RESULTS
In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire.
CONCLUSION
BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.
Topics: Humans; Influenza, Human; Pyridones; Antiviral Agents; Triazines; Dibenzothiepins; Female; Male; Oseltamivir; Adult; Family Characteristics; Adolescent; Child; Middle Aged; Young Adult; Post-Exposure Prophylaxis; Child, Preschool; Morpholines; Thiepins; Double-Blind Method; Infant; Pyridines; Aged; Oxazines
PubMed: 38706384
DOI: 10.1111/irv.13302 -
Natural Products and Bioprospecting May 2024Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla...
Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC = 20.47 μM) compared to the positive control oseltamivir (IC = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.
PubMed: 38691189
DOI: 10.1007/s13659-024-00448-w -
Journal of Intensive Medicine Apr 2024Influenza pandemics are unpredictable recurrent events with global health, economic, and social consequences. The objective of this review is to provide an update on the... (Review)
Review
Influenza pandemics are unpredictable recurrent events with global health, economic, and social consequences. The objective of this review is to provide an update on the latest developments in early diagnosis and specific treatment of the disease and its complications, particularly with regard to respiratory organ failure. Despite advances in treatment, the rate of mortality in the intensive care unit remains approximately 30%. Therefore, early identification of potentially severe viral pneumonia is extremely important to optimize treatment in these patients. The pathogenesis of influenza virus infection depends on viral virulence and host response. Thus, in some patients, it is associated with an excessive systemic response mediated by an authentic cytokine storm. This process leads to severe primary pneumonia and acute respiratory distress syndrome. Initial prognostication in the emergency department based on comorbidities, vital signs, and biomarkers (e.g., procalcitonin, ferritin, human leukocyte antigen-DR, mid-regional proadrenomedullin, and lactate) is important. Identification of these biomarkers on admission may facilitate clinical decision-making to determine early admission to the hospital or the intensive care unit. These decisions are reached considering pathophysiological circumstances that are associated with a poor prognosis (e.g., bacterial co-infection, hyperinflammation, immune paralysis, severe endothelial damage, organ dysfunction, and septic shock). Moreover, early implementation is important to increase treatment efficacy. Based on a limited level of evidence, all current guidelines recommend using oseltamivir in this setting. The possibility of drug resistance should also be considered. Alternative options include other antiviral drugs and combination therapies with monoclonal antibodies. Importantly, it is not recommended to use corticosteroids in the initial treatment of these patients. Furthermore, the implementation of supportive measures for respiratory failure is essential. Current recommendations are limited, heterogeneous, and not regularly updated. Early intubation and mechanical ventilation is the basic treatment for patients with severe respiratory failure. Prone ventilation should be promptly performed in patients with acute respiratory distress syndrome, while early tracheostomy should be considered in case of planned prolonged mechanical ventilation. Clinical trials on antiviral treatment and respiratory support measures specifically for these patients, as well as specific recommendations for different at-risk populations, are necessary to improve outcomes.
PubMed: 38681787
DOI: 10.1016/j.jointm.2023.09.006 -
Viruses Apr 2024This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific... (Review)
Review
This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific therapeutics are described in alphabetical order including classic antiviral drugs, such as acyclovir, abacavir, adefovir, amantadine, didanosine, entecavir, ganciclovir, interferon, lamivudine, penciclovir, famciclovir, oseltamivir, ribavirin, and zidovudine, repurposed drugs, such as ivermectin and nitazoxanide, which were originally used as antiparasitic drugs, and some others substances showing antiviral activity, such as ampligen, azo derivates, docosanol, fluoroarabinosylpyrimidine nucleosides, and novel peptides. Most of them have only been used for research purposes and are not widely used in clinical practice because of a lack of essential pharmacokinetic and safety data. Suggested future research directions are also highlighted.
Topics: Antiviral Agents; Animals; Birds; Virus Diseases; Bird Diseases; Poultry
PubMed: 38675934
DOI: 10.3390/v16040593 -
Pharmacotherapy May 2024To determine whether there is a signal for gastrointestinal (GI) or intracranial (IC) hemorrhage associated with the use of antiviral medications for influenza in the US...
STUDY OBJECTIVE
To determine whether there is a signal for gastrointestinal (GI) or intracranial (IC) hemorrhage associated with the use of antiviral medications for influenza in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.
DESIGN
Disproportionality analysis.
DATA SOURCE
The FAERS database was searched using OpenVigil 2.1 to identify GI and IC hemorrhage events reported between 2004 and 2022.
MEASUREMENTS
Antiviral medications for influenza included the following: oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Hemorrhage events were identified using Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries for GI and IC hemorrhages. Reporting odds ratios (RORs) were calculated to compare the occurrence of GI and IC hemorrhage events between antiviral drugs for influenza and (i) all other medications and (ii) antibiotics. RORs were also calculated for each of the individual antiviral medications.
MAIN RESULTS
A total of 245 cases of GI hemorrhage and 23 cases of IC hemorrhage were identified in association with four antivirals. In comparison with all other drugs, the RORs of GI hemorrhage for oseltamivir, zanamivir, peramivir, baloxavir, and all antivirals combined were 1.17, 0.62, 4.44, 2.53, and 1.22, respectively, indicating potential variations in GI hemorrhage risk among the antivirals. In contrast, in comparison with all other drugs, the RORs of IC hemorrhage for oseltamivir (0.44), zanamivir (0.16), baloxavir (0.44), and all antivirals combined (0.41) were less than 1.0 which is consistent with no elevated risk of IC hemorrhage.
CONCLUSION
In this study, some signals for GI hemorrhage were observed, particularly for peramivir and baloxavir marboxil. Further investigation is warranted to better understand and evaluate the potential risks of GI hemorrhage associated with antiviral treatments for influenza.
Topics: Humans; Antiviral Agents; United States; Adverse Drug Reaction Reporting Systems; United States Food and Drug Administration; Influenza, Human; Gastrointestinal Hemorrhage; Databases, Factual; Oseltamivir; Dibenzothiepins; Acids, Carbocyclic; Intracranial Hemorrhages; Zanamivir; Triazines; Middle Aged; Male; Guanidines; Morpholines; Pyridones; Female; Adult; Aged
PubMed: 38656741
DOI: 10.1002/phar.2920 -
Frontiers in Medicine 2024To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.
OBJECTIVE
To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.
METHODS
According to a random sequence generated by computer software, 200 patients with confirmed influenza A were divided into a study group and a control group with 100 cases in each group. Group allocation was concealed using sealed envelopes. The study group was treated with oral administration of baloxavir marboxil tablets, 40 mg once. The control group was given oral oseltamivir capsules, 75 mg twice a day, for five consecutive days. The therapeutic effects, symptom disappearance time and adverse drug reactions of the two groups after 5 days of treatment were compared.
RESULTS
There was no significant difference in the total effective rate between the two groups (99% vs. 98%, > 0.05). There was no significant difference in fever subsidence time (1.54 ± 0.66 d vs. 1.67 ± 0.71 d, > 0.05), cough improvement time (2.26 ± 0.91 d vs. 2.30 ± 0.90 d, > 0.05) and sore throat improvement time (2.06 ± 0.86 d vs. 2.09 ± 0.83 d, > 0.05) between the two groups. There was no significant difference in the incidence of adverse drug reactions between the two groups (8% vs. 13%, > 0.05).
CONCLUSION
Baloxavir marboxil tablets can be effectively used in the treatment of patients with influenza A and have a similar efficacy and safety profile as oseltamivir capsules.
PubMed: 38646560
DOI: 10.3389/fmed.2024.1339368 -
Communications Biology Apr 2024Since late 2021, highly pathogenic avian influenza (HPAI) viruses of A/goose/Guangdong/1/1996 (H5N1) lineage have caused widespread mortality in wild birds and poultry...
Since late 2021, highly pathogenic avian influenza (HPAI) viruses of A/goose/Guangdong/1/1996 (H5N1) lineage have caused widespread mortality in wild birds and poultry in the United States. Concomitant with the spread of HPAI viruses in birds are increasing numbers of mammalian infections, including wild and captive mesocarnivores and carnivores with central nervous system involvement. Here we report HPAI, A(H5N1) of clade 2.3.4.4b, in a common bottlenose dolphin (Tursiops truncatus) from Florida, United States. Pathological findings include neuronal necrosis and inflammation of the brain and meninges, and quantitative real time RT-PCR reveal the brain carried the highest viral load. Virus isolated from the brain contains a S246N neuraminidase substitution which leads to reduced inhibition by neuraminidase inhibitor oseltamivir. The increased prevalence of A(H5N1) viruses in atypical avian hosts and its cross-species transmission into mammalian species highlights the public health importance of continued disease surveillance and biosecurity protocols.
Topics: Animals; Influenza in Birds; Influenza A Virus, H5N1 Subtype; Bottle-Nosed Dolphin; Florida; Neuraminidase; Influenza A virus; Birds
PubMed: 38637646
DOI: 10.1038/s42003-024-06173-x -
Current Pharmaceutical Design Apr 2024Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been...
BACKGROUND
Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been reported that one hundred million people in the world are infected with influenza viruses, and two hundred and fifty thousand to five hundred thousand people die from the flu per year. In 2021, the number of infected persons in China was reported to be 654,700, and 0.07% of the infected persons died. The flu has caused a serious threat to human survival. Although several drugs, such as Zanamivir, Oseltamivir, Peramivir, and Laninamivir, have been used in clinics for the treatment of the influenza virus, there are some shortcomings of these drugs. The strain of influenza H5N1 (avian influenza) has been found to resist the effective drug Oseltamivir. Thus, there is an urgent demand to discover new anti-influenza virus inhibitors to overcome the emergence of influenza antigens.
AIMS
This study aimed to develop new anti-influenza virus inhibitors based on the rupestonic acid parent core.
OBJECTIVE
The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized in this work for the development of anti-influenza virus inhibitors.
METHODS
The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials. Their structures were characterized by 1H NMR and 13C NMR, and the purity was determined by HPLC. Then, their preliminary in vitro anti-influenza activity was evaluated using Oseltamivir as a reference drug.
RESULTS
The results showed that the synthesized rupestonic acid L-ephedrine derivatives A and B were more potent anti-influenza virus agents against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) with the IC50 values of 51.0, 51.0 μM and 441.0, 441.0 μM, respectively, than that of rupestonic acid. By comparing the IC50 of compounds A and B, compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors.
CONCLUSION
The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using 1H NMR and 13C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of anti-influenza inhibitors.
PubMed: 38623973
DOI: 10.2174/0113816128282194240329045625 -
Bioorganic & Medicinal Chemistry Letters Jun 2024Neuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through...
Neuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through pharmacophore-based virtual screening and molecular dynamics simulation, and 14 new compounds were obtained by modifying the lead compound 5 based on pharmacophore features. The biological activity test shows that 5n (IC = 0.13 μM) has a better inhibitory effect on wild-type NA (H5N1), while 5i (IC = 0.44 μM) has a prominent inhibitory effect on mutant NA (H5N1-H274Y), both of them are better than the positive control oseltamivir carboxylate (OSC). The analysis of docking results indicate that the good activities of compounds 5n and 5i may be attributed to the thiophene ring in 5n can stretch into the 150-cavity of NA, whereas the thiophene moiety in 5i can extend to the 430-cavity of NA. The findings of this study may be helpful for the discovery of new NA inhibitors.
Topics: Neuraminidase; Enzyme Inhibitors; Antiviral Agents; Structure-Activity Relationship; Hydrazones; Influenza A Virus, H5N1 Subtype; Drug Discovery; Molecular Docking Simulation; Molecular Structure; Humans; Molecular Dynamics Simulation; Dose-Response Relationship, Drug
PubMed: 38608962
DOI: 10.1016/j.bmcl.2024.129743