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Published on: February 4, 2012
Resistant influenza A viruses in children treated with oseltamivir: descriptive study
Maki Kiso1, Keiko Mitamura, Yuko Sakai-Tagawa
1Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
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.
Insights
Oseltamivir-resistant influenza mutants are more common in children than previously thought. Children can transmit these resistant viruses even after five days of treatment.
Area of Science:
- Virology
- Antiviral Resistance
- Pediatric Infectious Diseases
Background:
- Oseltamivir is a key neuraminidase inhibitor for influenza treatment.
- Limited data exists on oseltamivir resistance in children during clinical use.
- This study addresses the gap in understanding resistance development in pediatric influenza cases.
Purpose of the Study:
- To investigate the emergence of oseltamivir resistance in pediatric influenza patients.
- To characterize the specific mutations conferring resistance.
- To assess the duration of viral shedding in treated children.
Main Methods:
- Analysis of influenza A (H3N2) viruses from 50 children before and during oseltamivir treatment.
- Sequencing of neuraminidase and haemagglutinin genes.
- Phenotypic testing of mutant neuraminidases against oseltamivir carboxylate.
Main Results:
- Neuraminidase mutations conferring resistance were found in 18% of patients.
- Common mutations included Arg292Lys, Glu119Val, and Asn294Ser, increasing resistance significantly.
- Oseltamivir-resistant viruses were detected from day 4 of treatment onwards.
Conclusions:
- Oseltamivir-resistant influenza mutants emerge more frequently in children than previously reported.
- Children can act as a source for transmitting drug-resistant influenza strains.
- Findings highlight the need for monitoring antiviral resistance in pediatric populations.
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