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Clin Infect Dis. 2019 Sep 27. pii: ciz939. doi: 10.1093/cid/ciz939. [Epub ahead of print]

Viral Kinetics and Resistance Development in Children Treated with Neuraminidase Inhibitors: The Influenza Resistance Information Study (IRIS).

Author information

1
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
2
Micron Research Ltd, Ely, UK.
3
Roche Products Ltd, Welwyn Garden City, UK.
4
Clinical Virology and Diagnostics, Alkmaar, The Netherlands.
5
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
6
University Health Network, Toronto, ON, Canada.
7
Department of Pediatrics, Microbiology, Medicine and Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA.
8
School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
9
Research Institute for Infectious Diseases and Zoonosis, University of Veterinary Medicine, Hannover, Germany.
10
Artemis One Health Foundation, Utrecht, The Netherlands.
11
Department of Pediatrics, Subdivision Infectious Diseases and Immunology, Erasmus Medical Center - Sophia, Rotterdam, The Netherlands.

Abstract

BACKGROUND:

The effect of age, baseline viral load, vaccination status, antiviral therapy and emergence of drug resistance on viral shedding in children infected with influenza A or B virus was studied.

METHODS:

Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study (IRIS; NCT00884117) were analyzed by polymerase chain reaction to determine the influenza virus(sub-)type, viral load and resistance mutations. Disease severity was assessed; clinical symptoms were recorded. The association of age with viral load and viral clearance was examined by determining the area under the curve for viral RNA shedding using logistic regression and Kaplan-Meier analyses.

RESULTS:

A total of 2131 children infected with influenza (683 A/H1N1pdm09; 825 A/H3N2; 623 influenza B) were investigated. Age did not affect the mean baseline viral load. Children aged 1>5 years, infected with A/H1N1pdm09, A/H3N2 or influenza B virus had prolonged viral RNA shedding (±1-2 days) compared with older children (aged >5 years) and up to 1.2-fold higher total viral burden. Besides older age (odds ratio [OR] 1.08; confidence interval [CI]: 1.05-1.12), prior vaccination status (OR 1.72; CI: 1.22-2.43) and antiviral treatment (OR 1.74; CI: 1.43-2.12) increased the rate of viral clearance. Resistance mutations were detected in 49 children infected with influenza A virus (34 A/H1N1pdm09; 15 A/H3N2) treated with oseltamivir, most of whom were aged <5 years (n = 39).

CONCLUSIONS:

Children aged 1>5 years had a higher total viral burden with prolonged virus shedding and had an increased risk of acquiring resistance mutations following antiviral treatment.

KEYWORDS:

Influenza; Influenza Resistance Information Study; pediatrics; resistance mutations; viral load

PMID:
31560055
DOI:
10.1093/cid/ciz939

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