Viral Kinetics and Resistance Development in Children Treated with Neuraminidase Inhibitors: The Influenza Resistance
Rueshandra Roosenhoff1, Vaughan Reed2, Andy Kenwright3
1Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Insights
Young children (1-5 years) shed influenza virus longer and have a higher viral burden. Antiviral treatment and vaccination improve viral clearance, but younger children face higher resistance mutation risks.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Epidemiology
Background:
- Influenza virus infections are common in children.
- Factors influencing viral shedding and clearance in pediatric populations require further investigation.
- Understanding drug resistance emergence is crucial for effective treatment.
Purpose of the Study:
- To investigate the impact of age, viral load, vaccination, antiviral therapy, and drug resistance on influenza viral shedding in children.
- To analyze factors affecting viral clearance and resistance mutation development.
Main Methods:
- Polymerase chain reaction (PCR) was used to analyze samples from 2131 children (aged ≤13 years) over 7 years.
- Viral (sub-)type, viral load, and resistance mutations were determined.
- Logistic regression and Kaplan-Meier analyses examined associations between age, viral load, and viral clearance.
Main Results:
- Children aged 1-5 years exhibited prolonged viral RNA shedding (1-2 days longer) and a 1.2-fold higher total viral burden.
- Older age, prior vaccination, and antiviral treatment were associated with increased rates of viral clearance.
- Resistance mutations were found in 49 children with influenza A, primarily those under 5 treated with oseltamivir.
Conclusions:
- Younger children (1-5 years) experience prolonged influenza virus shedding and higher viral burden.
- Antiviral treatment and vaccination enhance viral clearance in children.
- Young children treated with antivirals have an elevated risk of developing influenza resistance mutations.
Background:
We studied 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.
Methods:
Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study were analyzed using 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 had prolonged viral RNA shedding (±1-2 days) compared with older children and up to 1.2-fold higher total viral burden. Besides, in 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.
Clinical Trials Registration:
NCT00884117.
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