Virus Load Kinetics and Resistance Development During Oseltamivir Treatment in Infants and Children Infected With Influenza A(H1N1) 2009 and Influenza B Viruses

Rath, Barbara; Kleist, Max von; Tief, Franziska; Karsch, Katharina; Tuerk, Ewelina; Muehlhans, Susann; Louis, Florian; Skopnik, H.; Schweiger, Brunhilde; Duwe, Susanne

doi:10.1097/inf.0b013e31825c7304

Cited by 27 publications

(36 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From October 1, 2011 to April 30, 2013, all patients fulfilling pre-defined criteria for influenza-like illness (fever ≥38°C and ≥ one respiratory sign or symptom) were assessed consecutively by a specifically trained QM team [7], [21]. Cases were included if i) the patient was 0–18 years of age, and ii) influenza infection was confirmed by RT-PCR in the national reference laboratory.…”

Section: Methodsmentioning

confidence: 99%

“…Qualitative and quantitative RT-PCR were performed as described recently [7]. Briefly, nasopharyngeal swabs were washed out in cell culture medium and RNA was extracted either by using the MagAttract Viral RNA 48 Kit (Qiagen), the RTP RNA/DNA Virus Minikit (Invitek), or the MagnaPure 96 DNA and viral NA small volume kit (Roche).…”

Section: Methodsmentioning

confidence: 99%

“…Immediate assessments would be particularly important in the inpatient setting and during the peak of flu season, when infection control measures are increasingly challenging and many different physicians may be assessing the patient over time. In influenza patients receiving antiviral therapy, an objective POC measure of viral load should be able to discriminate treatment success from virologic failure, which may contribute to the emergence of drug resistance [7]. WHO and CDC guidelines recommend extending the duration of antiviral therapy beyond five days in influenza patients with evidence of ongoing viral replication, immuno-compromise or severe illness (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…ICU-level care) [8], [9]. Considering the possibility of antiviral resistance and viral rebound with premature termination of treatment, simple means of estimating viral clearance in high-risk patients are needed [7], [10]–[13]. Furthermore, clinical trials evaluating newly developed antivirals will require objective parameters to evaluate antiviral efficacy compared to, or in combination with, currently available drugs [12], [14].…”

Section: Introductionmentioning

confidence: 99%

“…Rapid antigen test may be able to fill this gap. During the process of viral clearance, the loss of antigen-positivity may indicate successful treatment or “overcoming” of natural infection, whereas RT-PCR results tend to remain positive for extended periods of time, even beyond resolution of clinical symptoms [7].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Quantitative Influenza Follow-Up Testing (QIFT)—A Novel Biomarker for the Monitoring of Disease Activity at the Point-of-Care

Chen

Yousef²,

Duwe

et al. 2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

BackgroundInfluenza infections induce considerable disease burden in young children. Biomarkers for the monitoring of disease activity at the point-of-care (POC) are currently lacking. Recent methodologies for fluorescence-based rapid testing have been developed to provide improved sensitivities with the initial diagnosis. The present study aims to explore the utility of second-generation rapid testing during longitudinal follow-up of influenza patients (Rapid Influenza Follow-up Testing = RIFT). Signal/control fluorescent readouts (Quantitative Influenza Follow-up Testing = QIFT) are evaluated as a potential biomarker for the monitoring of disease activity at the POC.Methods and FindingsRIFT (SOFIA) and QIFT were performed at the POC and compared to blinded RT-PCR at the National Reference Centre for Influenza. From 10/2011-4/2013, a total of 2048 paediatric cases were studied prospectively; 273 cases were PCR-confirmed for influenza. During follow-up, RIFT results turned negative either prior to PCR (68%), or simultaneously (30%). The first negative RIFT occurred after a median of 8 days with a median virus load (VL) of 5.6×10∧3 copies/ml and cycle threshold of 37, with no evidence of viral rebound. Binning analysis revealed that QIFT differentiated accurately between patients with low, medium and high viral titres. QIFT increase/decrease showed 88% agreement (sensitivity = 52%, specificity = 95%) with VL increase/decrease, respectively. QIFT-based viral clearance estimates showed similar values compared to PCR-based estimates. Variations in viral clearance rates were lower in treated compared to untreated patients. The study was limited by use of non-invasive, semi-quantitative nasopharyngeal samples. VL measurements below the limit of detection could not be quantified reliably.ConclusionsDuring follow-up, RIFT provides a first surrogate measure for influenza disease activity. A “switch” from positive to negative values may indicate a drop in viral load below a critical threshold, where rebound is no longer expected. QIFT may provide a useful tool for the monitoring of disease burden and viral clearance at the POC.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Quantitative Influenza Follow-Up Testing (QIFT)—A Novel Biomarker for the Monitoring of Disease Activity at the Point-of-Care

Chen

Yousef²,

Duwe

et al. 2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review

Conrad

Alchikh

et al. 2018

Reviews in Medical Virology

Self Cite

View full text Add to dashboard Cite

Studies have shown that the predictive value of "clinical diagnoses" of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence-based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus-1, coronaviruses, or parainfluenza virus: (a) systematic review and meta-analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data-driven analysis of an inception cohort of 6073 children with ILI (aged 0-18 years, 56% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our "real-world" dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms.

show abstract

Targeting the Skin for Microneedle Delivery of Influenza Vaccine

Koutsonanos

Compans

Skountzou

2013

Crossroads Between Innate and Adaptive Immunity IV

View full text Add to dashboard Cite

Influenza infection represents a major socioeconomic burden worldwide. Skin represents a new target that has gained much attention in recent years for delivery of influenza vaccine as an alternative to the conventional intramuscular route of immunization. In this review we describe different microneedle vaccination approaches used in vivo, including metal and dissolving microneedle patches that have demonstrated promising results. Additionally we analyze the immunological basis for microneedle skin immunization and targeting of the skin's dense population of antigen presenting cells, their role, characterization, and function. Additionally we analyze the importance of inflammatory signaling in the skin after microneedle delivery.

show abstract

Virus Load Kinetics and Resistance Development During Oseltamivir Treatment in Infants and Children Infected With Influenza A(H1N1) 2009 and Influenza B Viruses

Cited by 27 publications

References 27 publications

Quantitative Influenza Follow-Up Testing (QIFT)—A Novel Biomarker for the Monitoring of Disease Activity at the Point-of-Care

Quantitative Influenza Follow-Up Testing (QIFT)—A Novel Biomarker for the Monitoring of Disease Activity at the Point-of-Care

Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review

Targeting the Skin for Microneedle Delivery of Influenza Vaccine

Contact Info

Product

Resources

About