Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004;364(9436):759-65.
doi: 10.1016/S0140-6736(04)16934-1.

Resistant influenza A viruses in children treated with oseltamivir: descriptive study

Maki Kiso  1 , Keiko Mitamura, Yuko Sakai-Tagawa, Kyoko Shiraishi, Chiharu Kawakami, Kazuhiro Kimura, Frederick G Hayden, Norio Sugaya, Yoshihiro Kawaoka
Affiliations

Resistant influenza A viruses in children treated with oseltamivir: descriptive study

Maki Kiso et al. Lancet. 2004.

Abstract

Background: Oseltamivir is an effective inhibitor of influenza virus neuraminidase. Although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. Our aim was to investigate oseltamivir resistance in a group of children treated for influenza.

Methods: We analysed influenza A viruses (H3N2) collected from 50 children before and during treatment with oseltamivir. We sequenced the genes for neuraminidase and haemagglutinin and studied the mutant neuraminidases for their sensitivity to oseltamivir carboxylate.

Findings: We found neuraminidase mutations in viruses from nine patients (18%), six of whom had mutations at position 292 (Arg292Lys) and two at position 119 (Glu119Val), which are known to confer resistance to neuraminidase inhibitors. We also identified another mutation (Asn294Ser) in one patient. Sensitivity testing to oseltamivir carboxylate revealed that the neuraminidases of viruses that have an Arg292Lys, Glu119Val, or Asn294Ser mutation were about 10(4)-10(5)-fold, 500-fold, or 300-fold more resistant than their pretreatment neuraminidases, respectively. Oseltamivir-resistant viruses were first detected at day 4 of treatment and on each successive day of the study. More than 10(3) infectious units per mL of virus were detected in some of the patients who did not shed drug-resistant viruses, even after 5 days of treatment.

Interpretation: Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir.

PubMed Disclaimer

Comment in

  • Oseltamivir-resistant influenza?
    Moscona A. Moscona A. Lancet. 2004 Aug 28-Sep 3;364(9436):733-4. doi: 10.1016/S0140-6736(04)16947-X. Lancet. 2004. PMID: 15337382 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources