Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons

Monto, Arnold S.; Malosh, Ryan E.; Petrie, Joshua G.; Thompson, Mark G.; Ohmit, Suzanne E.

doi:10.1093/infdis/jiu327

Cited by 94 publications

(129 citation statements)

References 36 publications

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“…Parents need encouragement and support when keeping track of the vaccination record of their children (Thorpe et al, 2016, Varkey et al, 2010). This may be particularly important in larger families with many children (Byington et al, 2015, Monto et al, 2014, Pearce et al, 2015, Amin et al, 2013, Oliveira et al, 2014). Current vaccination records however, are not designed to be used or understood by lay people.…”

Section: Discussionmentioning

confidence: 99%

Educating parents about the vaccination status of their children: A user-centered mobile application

Seeber

Conrad

Hoppe

et al. 2017

Preventive Medicine Reports

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Parents are often uncertain about the vaccination status of their children. In times of vaccine hesitancy, vaccination programs could benefit from active patient participation. The Vaccination App (VAccApp) was developed by the Vienna Vaccine Safety Initiative, enabling parents to learn about the vaccination status of their children, including 25 different routine, special indication and travel vaccines listed in the WHO Immunization Certificate of Vaccination (WHO-ICV). Between 2012 and 2014, the VAccApp was validated in a hospital-based quality management program in Berlin, Germany, in collaboration with the Robert Koch Institute. Parents of 178 children were asked to transfer the immunization data of their children from the WHO-ICV into the VAccApp. The respective WHO-ICV was photocopied for independent, professional data entry (gold standard). Demonstrating the status quo in vaccine information reporting, a Recall Group of 278 parents underwent structured interviews for verbal immunization histories, without the respective WHO-ICV. Only 9% of the Recall Group were able to provide a complete vaccination status; on average 39% of the questions were answered correctly. Using the WHO-ICV with the help of the VAccApp resulted in 62% of parents providing a complete vaccination status; on average 95% of the questions were answered correctly. After using the VAccApp, parents were more likely to remember key aspects of the vaccination history. User-friendly mobile applications empower parents to take a closer look at the vaccination record, thereby taking an active role in providing accurate vaccination histories. Parents may become motivated to ask informed questions and to keep vaccinations up-to-date.

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Section: Discussionmentioning

confidence: 99%

Educating parents about the vaccination status of their children: A user-centered mobile application

Seeber

Conrad

Hoppe

et al. 2017

Preventive Medicine Reports

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“…Patient-derived samples of influenza A virus were collected as part of the Household Influenza Vaccine Effectiveness (HIVE) study (39,40) and kindly provided by Arnold S. Monto and colleagues at the University of Michigan School of Public Health. The HIVE study was approved by the Institutional Review Board at the University of Michigan, and all subjects provided informed consent.…”

Section: Methodsmentioning

confidence: 99%

Measurements of Intrahost Viral Diversity Are Extremely Sensitive to Systematic Errors in Variant Calling

McCrone

Lauring

2016

J Virol

115

164

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With next-generation sequencing technologies, it is now feasible to efficiently sequence patient-derived virus populations at a depth of coverage sufficient to detect rare variants. However, each sequencing platform has characteristic error profiles, and sample collection, target amplification, and library preparation are additional processes whereby errors are introduced and propagated. Many studies account for these errors by using ad hoc quality thresholds and/or previously published statistical algorithms. Despite common usage, the majority of these approaches have not been validated under conditions that characterize many studies of intrahost diversity. Here, we use defined populations of influenza virus to mimic the diversity and titer typically found in patient-derived samples. We identified single-nucleotide variants using two commonly employed variant callers, Deep-SNV and LoFreq. We found that the accuracy of these variant callers was lower than expected and exquisitely sensitive to the input titer. Small reductions in specificity had a significant impact on the number of minority variants identified and subsequent measures of diversity. We were able to increase the specificity of DeepSNV to >99.95% by applying an empirically validated set of quality thresholds. When applied to a set of influenza virus samples from a household-based cohort study, these changes resulted in a 10-fold reduction in measurements of viral diversity. We have made our sequence data and analysis code available so that others may improve on our work and use our data set to benchmark their own bioinformatics pipelines. Our work demonstrates that inadequate quality control and validation can lead to significant overestimation of intrahost diversity. IMPORTANCEAdvances in sequencing technology have made it feasible to sequence patient-derived viral samples at a level sufficient for detection of rare mutations. These high-throughput, cost-effective methods are revolutionizing the study of within-host viral diversity. However, the techniques are error prone, and the methods commonly used to control for these errors have not been validated under the conditions that characterize patient-derived samples. Here, we show that these conditions affect measurements of viral diversity. We found that the accuracy of previously benchmarked analysis pipelines was greatly reduced under patientderived conditions. By carefully validating our sequencing analysis using known control samples, we were able to identify biases in our method and to improve our accuracy to acceptable levels. Application of our modified pipeline to a set of influenza virus samples from a cohort study provided a realistic picture of intrahost diversity and suggested the need for rigorous quality control in such studies. Many viral pathogens are thought to exist as a cloud of closely related mutants within an infected individual (1). Until recently, our understanding of intrahost viral dynamics and the impact of viral diversity on evolution and pathogenesis has been li...

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“…Incomplete immunity results in continued susceptibility to reinfection through life. For example, we recently detected RSV in 4% of acute respiratory illnesses (ARI) in community dwelling adults 18-49 years old [11]. Current vaccine development efforts have identified prevention of severe RSV-associated illness in older adults, particularly those resulting in hospitalization, as a priority.…”

Section: Introductionmentioning

confidence: 99%

Respiratory syncytial virus hospitalization in middle-aged and older adults

Malosh

Martin

Callear

et al. 2017

Journal of Clinical Virology

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Background The importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those ≥ 65 years. Objectives We sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults ≥18 years. Study Design Adults hospitalized with acute respiratory illnesses (ARI) of ≤10 days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons. Collected specimens were tested for RSV and influenza by real-time, reverse transcription polymerase chain reaction (RT-PCR). Viral load and subtype were determined for RSV-positive specimens. We evaluated factors associated with RSV and outcomes of infection using multivariable logistic regression. RSV-positive patients were separately compared to two reference groups: RSV-negative and influenza-negative, and influenza-positive patients. Results RSV was detected in 84 (7%) of 1259 hospitalized individuals (55 RSV-B, 29 RSV-A). The highest prevalence was found in 50-64 year olds (40/460; 8.7%); 98% of RSV cases in this age group had at least one chronic comorbidity. RSV detection was associated with obesity (OR: 1.71 95% CI: 0.99-3.06, p=0.03). Individuals with RSV were admitted to the hospital later in their illness and had a higher median Charlson comborbidity index (3 vs 2 p < 0.001) compared to those with influenza. Clinical severity of RSV-associated hospitalizations was similar to influenza-associated hospitalizations. Discussion In this study we observed the highest frequency of RSV-associated hospitalizations among adult 50-64 years old; many of whom had chronic comorbidities. Our results suggest the potential benefit of including these individuals in future RSV vaccination strategies.

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Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons

Abstract: Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI.

Cited by 94 publications

References 36 publications

Educating parents about the vaccination status of their children: A user-centered mobile application

Educating parents about the vaccination status of their children: A user-centered mobile application

Measurements of Intrahost Viral Diversity Are Extremely Sensitive to Systematic Errors in Variant Calling

Respiratory syncytial virus hospitalization in middle-aged and older adults

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