Treatment Of Severe Influenza Research Articles

Comparative effectiveness of oseltamivir versus peramivir for hospitalized children (aged 0-5 years) with influenza infection

ObjectivesThe effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV). MethodsWe analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated. ResultsChildren who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV. ConclusionOseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.

Clinical Effectiveness of Intravenous Peramivir Compared With Oseltamivir in Patients With Severe Influenza A With Primary Viral Pneumonia: A Randomized Controlled Study.

BackgroundHigh-quality evidence confirms that the clinical efficacy of peramivir in severe influenza patients with primary viral pneumonia is lacking. To optimize clinical medication, we evaluate the different efficacy between peramivir and oseltamivir in the treatment of severe influenza A with primary viral pneumonia.MethodsA single-center, randomized, controlled trial was conducted during the Chinese influenza season from December 2018 to April 2019 in patients with severe influenza A with primary viral pneumonia. A total of 40 inpatients were enrolled and treated with either intravenous peramivir (300 mg, once daily for 5 days) or oral oseltamivir (75 mg, twice daily for 5 days).ResultsThe duration of influenza virus nucleic acid positivity in the oseltamivir group and the peramivir group was 2.95 days and 2.80 days, respectively. The remission times of clinical symptoms in the oseltamivir group and the peramivir group were 3.90 days and 3.25 days, respectively. In addition, the remission time of cough symptoms in the peramivir group (63.89 hours) was shorter than that in the oseltamivir group (75.53 hours). There was no significant difference between these values (P > .05). The remission time of fever symptoms in the oseltamivir group was 23.67 hours, which was significantly longer than that in the peramivir group (12.32 hours) (P = .034).ConclusionsPeramivir is no less effective than oseltamivir in the treatment of severe influenza A with primary viral pneumonia, and patients treated with peramivir had significantly shorter remission times of fever symptoms than those treated with oseltamivir.

Progress in diagnosis and treatment of severe influenza in children

流行性感冒（简称流感）是儿童季节性高发传染病，重症流感发病率和病死率相对较高。肺炎仍然是儿童流感最常见的并发症,儿童流感相关性神经系统并发症的发病率明显高于成人，需引起重视。神经氨酸酶抑制剂仍是首选抗流感药物，但耐药问题应引起关注。除一般器官功能支持方法外，体外膜肺氧合在我国儿童重症流感中的应用逐步增多。国家卫生健康委员会颁布的"流行性感冒诊疗方案（2019年版)"对儿童重症流感的诊治给出了更详细的推荐。

Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series

BackgroundIntravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited.Case presentationWe report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures.The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections.ConclusionsIV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.

A Retrospective Analysis of Three Antiviral Regimens of Peramivir in the Treatment of Severe Influenza A with Primary Viral Pneumonia.

Objective To evaluate the difference of clinical efficacy of peramivir alone and peramivir combined with immunomodulators (either ribonucleic acid or thymopetidum) in the treatment of severe influenza A with primary viral pneumonia. Methods A retrospective analysis was applied to 45 patients who were diagnosed with severe influenza A with primary viral pneumonia in our hospital from December 2017 to March 2018. The cases were divided into three groups: the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group. Results The duration of viral nucleic acid positivity in the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 6.13 ± 2.06, 6.53 ± 2.72, and 6.10 ± 1.37 days, respectively. The remission time of the clinical symptoms of the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 8.06 ± 2.73, 7.94 ± 2.89, and 7.67 ± 1.58 days, respectively. Comparisons between the peramivir group and the peramivir combined with ribonucleic acid group or the peramivir combined with thymopetidum group revealed no significant differences in the duration of virus nucleic acid positivity, remission time of clinical symptoms, time to fever alleviation, and time to cough alleviation. Conclusions There is no observed benefit in the addition of ribonucleic acid or thymopetidum when peramivir sodium chloride injection is used in the treatment of severe influenza A with primary viral pneumonia. This trial is registered with ChiCTR1800019417.

Optimizing T-705 (favipiravir) treatment of severe influenza B virus infection in the immunocompromised mouse model.

Influenza B virus infections remain insufficiently studied and antiviral management in immunocompromised patients is not well defined. The treatment regimens for these high-risk patients, which have elevated risk of severe disease-associated complications, require optimization and can be partly addressed via animal models. We examined the efficacy of monotherapy with the RNA-dependent RNA polymerase inhibitor T-705 (favipiravir) in protecting genetically modified, permanently immunocompromised BALB scid mice against lethal infection with B/Brisbane/60/2008 (BR/08) virus. Beginning at 24 h post-infection, BALB scid mice received oral T-705 twice daily (10, 50 or 250 mg/kg/day) for 5 or 10 days. T-705 had a dose-dependent effect on survival after BR/08 challenge, resulting in 100% protection at the highest dosages. With the 5 day regimens, dosages of 50 or 250 mg/kg/day reduced the peak lung viral titres within the treatment window, but could not efficiently clear the virus after completion of treatment. With the 10 day regimens, dosages of 50 or 250 mg/kg/day significantly suppressed virus replication in the lungs, particularly at 45 days post-infection, limiting viral spread and pulmonary pathology. No T-705 regimen decreased virus growth in the nasal turbinates of mice, which potentially contributed to the viral dynamics in the lungs. The susceptibility of influenza B viruses isolated from T-705-treated mice remained comparable to that of viruses from untreated control animals. T-705 treatment is efficacious against lethal challenge with BR/08 virus in immunocompromised mice. The antiviral benefit was greatest when longer T-705 treatment was combined with higher dosages.

Pathogenesis of severe influenza in children

Children are at high risk for influenza and for severe cases.This article discussed the pathogenesis of severe influenza in children, including evaluation methods, immune system development, energy metabolism, genetic background and influenza virus strains.Try to provide some ideas for early identification, diagnosis and treatment of severe influenza in children. Key words: Influenza; Pathogenesis; Child

Developments in the treatment of severe influenza

Cases of severe influenza may occur during seasonal epidemics, following sporadic zoonotic influenza A transmission from animal reservoirs or on a massive scale with the unpredictable emergence of a new pandemic influenza strain. Clinical experience identifies unmet medical need for additional therapies for influenza, in particular to treat severely unwell adults and children. During and following the pandemic of 2009, a wealth of data from hospitalized cases of influenza from many different countries accumulated and are now starting to emerge. Observational clinical data provide information about the efficacy of existing antiviral drugs in severely ill patients. The development pipeline for new therapies contains several promising agents which are focussed on a range of viral targets, and opens the possibility of combination antiviral therapy for the first time, which may be especially useful in clinically challenging cases. Advances in immunological methods and recombinant protein engineering support the potential for use of immunomodulating therapies as adjuncts in treatment of severe influenza. The main themes are the importance of treating severe influenza early, considering multiple therapy options and the relevance of observational clinical data to treatment of severely ill and risk groups. Clinicians, who may have only seen the media headlines following discussion of reviews which deal with randomized controlled trials of neuraminidase inhibitor drug use in mild uncomplicated influenza in the community, may be hesitant to prescribe these drugs. Observational data arising from treatment of severely ill individuals support use of these drugs early in illness and show improvement in outcomes associated with drug use.

Seasonal Human Influenza: Treatment Options.

Opinion statementSeasonal influenza can be a self-limiting illness in healthy individuals but is associated with short-term morbidity and economic burden. Influenza can cause significant morbidity and mortality in young children, the elderly, pregnant and post-partum women, patients with co-morbidities and the immunocompromised. Neuraminidase inhibitors (NAIs) are the treatment of choice for influenza due to widespread resistance to the adamantanes. NAIs are efficacious for the treatment of influenza in ambulatory patients with mild illness, when initiated within 48 h of symptom onset. Early treatment with NAIs has been shown to reduce otitis media in children, and lower respiratory tract complications, resulting in antibiotic therapy, in adults. Evidence on the efficacy of NAIs for the prevention of influenza-related complications in at-risk populations, based on reviews of data from randomised trials is inconclusive. However, observational studies suggest that in hospitalised patients early treatment with NAIs has been associated with reduced mortality. NAIs should be initiated as soon as possible in patients at high-risk of influenza-related complications, with suspected or proven influenza, hospitalised patients and patients with severe or progressive disease. NAIs can be considered in previously healthy patients when therapy can be initiated within 48 h of symptom onset. In previously healthy patients, the therapeutic efficacy of oseltamivir is time-dependent, with maximal benefit observed when therapy is initiated within 48 h of symptom onset. However, several observational studies suggest therapeutic benefit beyond 48 h, in hospitalised patients, severe disease, and patients at high risk of complications, including pregnant women. NAIs should be considered in patients at high risk of influenza-related complications who present late. Further studies are needed to define the optimal timing of NAIs. Oseltamivir-resistant virus has been widely reported but is predominantly an issue in H1N1 seasonal influenza. Zanamivir-resistant influenza virus is rare, and inhaled or intravenous (IV) zanamivir is the treatment of choice in proven or suspected oseltamivir-resistant virus. Intubated patients with severe influenza can be treated with oseltamivir (suspension) administered via nasogastric tube. The commercial dry powder formulation of zanamivir should not be administered, via nebulisation, as it has been associated with ventilator malfunction and mortality. In intubated patients, when there are concerns about gastric absorption, IV zanamivir should be obtained under Emergency Investigational New Drug access schemes. Currently available evidence does not support the use of high-dose or extended-duration oseltamivir in patients with severe influenza, but does require further investigation. Extracorporeal membrane oxygenation has not been shown to be superior to conventional management in patients with influenza-associated acute respiratory distress syndrome and should be considered as salvage therapy. Corticosteriods should not be used in the treatment of severe influenza as this has been associated with increased risk of mortality and bacterial superinfection.

Treatment of Severe Cases of Pandemic (H1N1) 2009 Influenza: Review of Antivirals and Adjuvant Therapy

Three worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. In early March 2009, the first cases of influenza -like illness (ILI) were reported from Mexico. This strain was identified as influenza A/ H1N1 strain. Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. This review summarizes the recent patents for the use of antivirals in treatment of severe influenza.