#Effectiveness of four types of #neuraminidase #inhibitors approved in #Japan for the #treatment of #influenza (PLoS One, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

PLoS One. 2019 Nov 7;14(11):e0224683. doi: 10.1371/journal.pone.0224683. eCollection 2019.

Effectiveness of four types of neuraminidase inhibitors approved in Japan for the treatment of influenza.

Mawatari M1, Saito R1, Hibino A1, Kondo H1, Yagami R1, Odagiri T1,2, Tanabe I1, Shobugawa Y1; Japanese Influenza Collaborative Study Group.

Author information: 1 Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. 2 Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Iwate, Japan.




Neuraminidase inhibitors (NAIs) effectively treat influenza. The clinical effectiveness of four NAIs (oseltamivir, zanamivir, laninamivir, and peramivir) was evaluated against influenza A/H1N1pdm09, A/H3N2, and B viruses. Additionally, fever duration in patients infected with oseltamivir-resistant influenza A/H1N1pdm09 with the H275Y mutation was evaluated.


Patients aged <20 years who visited outpatient clinics in Japan with influenza-like illnesses were enrolled during 4 influenza seasons from 2012/2013 to 2015/2016. After obtaining informed consent, patients who tested positive for influenza with rapid tests received one of the four NAIs. Patients recorded their body temperature daily for 8 days from the first visit. The influenza strain was identified using real-time polymerase chain reaction. Univariate and multivariable analyses were used to evaluate factors influencing fever duration. In children aged ≤5 years treated with oseltamivir, fever duration in oseltamivir-resistant A/H1N1pdm09-infected patients was compared to that in oseltamivir-sensitive A/H1N1pdm09-infected patients.


Of the 1,368 patients analyzed, 297 (21.7%), 683 (49.9%), and 388 (28.4%) were infected with influenza A/H1N1pdm09, A/H3N2, and B, respectively. In multivariable analysis factors associated with significantly prolonged fever duration included: treatment with laninamivir (hazard ratio [HR]: 0.78, p = 0.006, compared to oseltamivir), influenza B (HR: 0.58, p<0.001, compared to influenza A/H1N1pdm09), and a higher body temperature at the clinic visit (HR: 0.87 per degree Celsius, p<0.001). Increasing age was associated with a significantly shorter duration of fever (HR: 1.31 for 6-9 years old, p<0.001; and HR: 1.65 for 10-19 years old, p<0.001, respectively, compared to 0-5 years old). Following treatment with oseltamivir, fever duration was significantly longer for oseltamivir-resistant A/H1N1pdm09-infected patients (n = 5) than for oseltamivir-sensitive A/H1N1pdm09 infected patients (n = 111) (mean, 89 versus 40 hours, p<0.001).


Our results revealed characteristic information on the effectiveness of the four NAIs and also on oseltamivir-resistant viruses that may affect patients’ clinical care.

PMID: 31697721 DOI: 10.1371/journal.pone.0224683

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Japan.


Use of #MRI in the #diagnosis and #prognosis of acute necrotizing #encephalopathy in a #Chinese teenager: A case report (Medicine (Baltimore), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Medicine (Baltimore). 2019 Nov;98(44):e17797. doi: 10.1097/MD.0000000000017797.

Use of MRI in the diagnosis and prognosis of acute necrotizing encephalopathy in a Chinese teenager: A case report.

Li H1, Sun C2, Chi S2, Wang Y2, Wu L3, Qin X3.

Author information: 1 Department of Magnetic Resonance Imaging. 2 Department of Intensive Care Unit. 3 Department of Neurology, People’s Hospital of RiZhao, Rizhao, China.




Acute necrotizing encephalopathy (ANE) is a rapidly progressing disease associated with frequent neurologic sequelae and has poor prognosis. Currently, the diagnosis and treatment of ANE rely on neuroradiologic findings and offering supportive care. Here, we report the successful treatment of a teenager diagnosed with ANE using combination of high-dose methylprednisolone and oseltamivir.


The patient, a 15-year-old female, presented with impaired consciousness and seizures secondary to acute upper respiratory tract infection. A series of brain magnetic resonance images (MRIs) were obtained toward establishing a possible diagnosis.


Based on the history of presenting illness and subsequent brain MRI scans, the patient was diagnosed to be suffering from ANE.


Following the diagnosis, the patient was placed on therapy comprising of high-dose methylprednisolone and oseltamivir.


After treatment with methylprednisolone and oseltamivir for 15 days, the patient recovered nearly completely from ANE as confirmed by subsequent brain MRI scans. No complications or other emerging clinical symptoms were noted for the duration of follow-up that lasted 6 months.


Contrary to common reports, ANE can occur beyond pediatric populations and its treatment should not be restricted to supportive care. Our case suggests that the use of high-dose corticosteroids and oseltamivir leads to promising prognosis.

PMID: 31689857 DOI: 10.1097/MD.0000000000017797

Keywords: Neurology; Neuroimaging; Antivirals; Corticosteroids; Oseltamivir; Encephalopathy.


#Influenza-associated #mortality in #hospital care: a retrospective cohort study of #risk #factors and impact of #oseltamivir in an #English teaching hospital, 2016 to 2017 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Influenza-associated mortality in hospital care: a retrospective cohort study of risk factors and impact of oseltamivir in an English teaching hospital, 2016 to 2017

Mark Reacher1,2, Ben Warne3, Lucy Reeve1, Neville Q. Verlander4, Nicholas K. Jones3, Kyriaki Ranellou3,5, Silvana Christou3, Callum Wright3, Saher Choudhry3, Maria Zambon6, Clare Sander3, Hongyi Zhang2, Hamid Jalal2

Affiliations: 1 Public Health England Field Service, Cambridge Institute of Public Health, Cambridge, United Kingdom; 2 Public Health England and Cambridge Universities Hospitals NHS Foundation Trust Cambridge, Cambridge, United Kingdom; 3 Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 4 Statistics Unit, Statistics, Modelling and Economics Department, National Infection Service – Data and Analytical Sciences, Public Health England, London, United Kingdom; 5 Division of Virology, Department of Pathology, University of Cambridge, United Kingdom; 6 National Infection Service, Public Health England, London, United Kingdom

Correspondence:  Mark Reacher

Citation style for this article: Reacher Mark, Warne Ben, Reeve Lucy, Verlander Neville Q., Jones Nicholas K., Ranellou Kyriaki, Christou Silvana, Wright Callum, Choudhry Saher, Zambon Maria, Sander Clare, Zhang Hongyi, Jalal Hamid. Influenza-associated mortality in hospital care: a retrospective cohort study of risk factors and impact of oseltamivir in an English teaching hospital, 2016 to 2017. Euro Surveill. 2019;24(44):pii=1900087. https://doi.org/10.2807/1560-7917.ES.2019.24.44.1900087

Received: 26 Jan 2019;   Accepted: 04 Sep 2019




Evidence of an oseltamivir treatment effect on influenza A(H3N2) virus infections in hospitalised patients is incomplete.


This cohort study aimed to evaluate risk factors for death among PCR-confirmed hospitalised cases of seasonal influenza A(H3N2) of all ages and the impact of oseltamivir.


Participants included all 332 PCR-confirmed influenza A(H3N2) cases diagnosed between 30 August 2016 and 17 March 2017 in an English university teaching Hospital. Oseltamivir treatment effect on odds of inpatient death was assessed by backward stepwise multivariable logistic regression analysis.


The odds of death were reduced by two thirds (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11–0.93), in inpatients treated with a standard course of oseltamivir 75 mg two times daily for 5 days – compared with those untreated with oseltamivir, after adjustment for age, sex, current excess alcohol intake, receipt of 2016/17 seasonal influenza vaccine, serum haemoglobin and hospital vs community attribution of acquisition of influenza.


Oseltamivir treatment given according to National Institutes of Clinical Excellence (NICE); United States Centres for Disease Control and Prevention (CDC); Infectious Diseases Society of America (IDSA) and World Health Organization (WHO) guidelines was shown to be effective in reducing the odds of mortality in inpatients with PCR-confirmed seasonal influenza A(H3N2) after adjustment in a busy routine English hospital setting. Our results highlight the importance of hospitals complying with relevant guidelines for prompt seasonal influenza PCR testing and ensuring standard oseltamivir treatment to all PCR-confirmed cases of seasonal influenza.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; Antivirals; Oseltamivir; England.


#Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose #Oseltamivir in Severely Immunocompromised #Children With #Influenza (Open Forum Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open Forum Infect Dis. 2019 Oct 23;6(10):ofz430. doi: 10.1093/ofid/ofz430. eCollection 2019 Oct.

Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose Oseltamivir in Severely Immunocompromised Children With Influenza.

Bautista F1, Engelhard D2, Rizzari C3, Baka M4, Saavedra-Lozano J5, Lopez-Medina E6, Nasmyth-Miller C7, Hernández-Sánchez J7, Sturm S8.

Author information: 1 Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. 2 Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 3 Pediatric Hematology-Oncology Unit, Department of Pediatrics, MBBM Foundation, ASST-Monza, University of Milano-Bicocca, Monza, Italy. 4 Department of Pediatric Oncology, Aglaia Kyriakou Children’s Hospital, Athens, Greece. 5 Infectious Disease Unit, Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 6 Department of Pediatrics, Universidad del Valle, Centro Médico Imbanaco and Centro de Estudios en Infectología Pediátrica, Cali, Colombia. 7 Roche Products Ltd, Welwyn Garden City, UK. 8 Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, Basel, Switzerland.



This randomized phase 1b study evaluated the pharmacokinetics/pharmacodynamics of conventional-dose (30-75 mg twice daily [BID]) vs triple-dose (90-225 mg BID; weight-adjusted) oseltamivir for treatment of influenza in severely immunocompromised children <13 years. Oseltamivir carboxylate (OC) Cmax and AUC0-12h were ~2-fold higher with triple-dose vs conventional-dose oseltamivir. Increased dose/exposure of oseltamivir/OC did not improve virological outcomes or reduce viral resistance. Median time to cessation of viral shedding was similar with triple-dose and conventional-dose oseltamivir (150.7 vs 157.1 hours, respectively); median time to alleviation of baseline fever was longer with conventional-dose oseltamivir (28.4 vs 11.3 hours). No new safety signals were identified.

© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

KEYWORDS: children; clinical trial; immunocompromised; influenza; oseltamivir

PMID: 31660381 PMCID: PMC6809794 DOI: 10.1093/ofid/ofz430

Keywords: Seasonal Influenza; Antivirals; Drugs Safety; Oseltamivir; Pediatrics.


#Oseltamivir Is Effective against 1918 #Influenza Virus Infection of #Macaques but Vulnerable to Escape (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape

Friederike Feldmann, Darwyn Kobasa, Carissa Embury-Hyatt, Allen Grolla, Tracy Taylor, Maki Kiso, Satoshi Kakugawa, Jason Gren, Steven M. Jones, Yoshihiro Kawaoka, Heinz Feldmann

Diane E. Griffin, Editor

DOI: 10.1128/mBio.02059-19



The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug.



Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Animal models; H1N1; Pandemic Influenza; Spanish flu.


#Neuraminidase #inhibitors susceptibility profiles of highly pathogenic #influenza A (#H5N1) viruses isolated from #avian species in #India (2006-2015) (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2018 Oct;158:143-146. doi: 10.1016/j.antiviral.2018.08.007. Epub 2018 Aug 17.

Neuraminidase inhibitors susceptibility profiles of highly pathogenic influenza A (H5N1) viruses isolated from avian species in India (2006-2015).

Sood R1, Kumar N2, Bhatia S2, Chanu KV2, Gupta CL3, Pateriya AK2, Mishra A2, Khandia R2, Mawale N2, Singh VP2.

Author information: 1 ICAR- National Institute of High Security Animal Diseases, Anand Nagar, Bhopal 462022, Madhya Pradesh, India. Electronic address: richa.sood@icar.gov.in. 2 ICAR- National Institute of High Security Animal Diseases, Anand Nagar, Bhopal 462022, Madhya Pradesh, India. 3 Department of Computer Science, University College London, Gower Street, WC1E 6BT, London, UK.



We tested 65 highly pathogenic avian influenza (HPAI) A(H5N1) viruses, isolated from avian species in India between 2006 and 2015, for susceptibility to the FDA approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir using a phenotypic fluorescence-based assay. The overall incidence of resistant variants among HPAI A(H5N1) viruses was 7.69% (5/65). The NA inhibition assay identified 3 viruses resistant to oseltamivir (N294S substitution, N2 numbering) and 2 cross-resistant to oseltamivir and zanamivir (E119A or I117V+E119A substitutions), all of which belonged to hemagglutinin (HA) clade 2.2 (5/17) and predominantly circulated in Indian poultry during 2006-2010. In comparison to E119A substitution alone, viruses with I117V+E119A double substitutions showed greater reduction in susceptibility to both oseltamivir and zanamivir. The NAI resistance-associated NA markers, identified in this study, were as a result of naturally occurring mutations. Of note, 48 viruses of HA clade that circulated in Indian poultry during 2011-2015 were susceptible to both oseltamivir and zanamivir. It is essential to monitor NAI susceptibility among human and avian HPAI A(H5N1) viruses that would provide baseline data to develop strategies for pandemic preparedness and therapeutic interventions.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS: HPAI A(H5N1) viruses; India; Neuraminidase inhibitors; Oseltamivir; Zanamivir

PMID: 30125616 DOI: 10.1016/j.antiviral.2018.08.007 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N1; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; India.


Effect of Oral #Oseltamivir on #Virological #Outcomes in Low-risk #Adults With #Influenza: A #RCT (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Jul 27. pii: ciz634. doi: 10.1093/cid/ciz634. [Epub ahead of print]

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Beigel JH1, Manosuthi W2, Beeler J3, Bao Y4, Hoppers M5, Ruxrungtham K6, Beasley RL7, Ison M8, Avihingsanon A6, Losso MH9, Langlois N10, Hoopes J11, Lane HC1, Holley HP3, Myers CA12, Hughes MD4, Davey RT4.

Author information: 1 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 2 Bamrasnaradura Infectious Diseases Institute, Department of Disease Control, Nonthaburi, Thailand. 3 Leidos Biomedical Research, Inc, Frederick, Maryland. 4 Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 5 Clinical Research Solutions, Jackson, Tennessee. 6 Department of Medicine, Faculty of Medicine, Chulalongkorn University, and Center for Biostatistics in AIDS Research, Human Immunodeficiency Virus Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand. 7 Health Concepts, Rapid City, South Dakota. 8 Department of Medicine, Northwestern University, Chicago, Illinois. 9 Immunocompromised Service, Hospital General De Agudos J. M. Ramos Mejía, Buenos Aires, Argentina. 10 Social & Scientific Systems, Inc, Silver Spring, Maryland. 11 AVR Laboratories LLC, Logan, Utah; and. 12 Operational Infectious Diseases, Naval Health Research Center, San Diego, California.




Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir’s ability to alter viral shedding.


From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3.


Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection.


Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms.


Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

KEYWORDS: influenza-like illness; respiratory virus; viral shedding

PMID: 31541242 DOI: 10.1093/cid/ciz634

Keywords: Seasonal Influenza; Antivirals; Oseltamivir.