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Institute
BACKGROUND:
Influenza-like illness (ILI) is a common reason for paediatric consultations. Viral causes predominate, but antibiotics are used frequently. With regard to influenza, pneumococcal coinfections are considered major contributors to morbidity/mortality.
METHODS:
In the context of a perennial quality management (QM) programme at the Charit{\'e} Departments of Paediatrics and Microbiology in collaboration with the Robert Koch Institute, children aged 0-18 years presenting with signs and symptoms of ILI were followed from the time of initial presentation until hospital discharge (Charit{\'e} Influenza-Like Disease = ChILD Cohort). An independent QM team performed highly standardized clinical assessments using a disease severity score based on World Health Organization criteria for uncomplicated and complicated/progressive disease. Nasopharyngeal and pharyngeal samples were collected for viral reverse transcription polymerase chain reaction and bacterial culture/sensitivity and MaldiTOF analyses. The term 'detection' was used to denote any evidence of viral or bacterial pathogens in the (naso)pharyngeal cavity. With the ChILD Cohort data collected, a standard operating procedure (SOP) was created as a model system to reduce the inappropriate use of antibiotics in children with ILI. Monte Carlo simulations were performed to assess cost-effectiveness.
RESULTS:
Among 2,569 ChILD Cohort patients enrolled from 12/2010 to 04/2013 (55\% male, mean age 3.2 years, range 0-18, 19\% {\ensuremath{>}}5 years), 411 patients showed laboratory-confirmed influenza, with bacterial co-detection in 35\%. Influenza and pneumococcus were detected simultaneously in 12/2,569 patients, with disease severity clearly below average. Pneumococcal vaccination rates were close to 90\%. Nonetheless, every fifth patient was already on antibiotics upon presentation; new antibiotic prescriptions were issued in an additional 20\%. Simulation of the model SOP in the same dataset revealed that the proposed decision model could have reduced the inappropriate use of antibiotics significantly (P{\ensuremath{<}}0.01) with an incremental cost-effectiveness ratio of -99.55?.
CONCLUSIONS:
Physicians should be made aware that in times of pneumococcal vaccination the prevalence and severity of influenza infections complicated by pneumococci may decline. Microbiological testing in combination with standardized disease severity assessments and review of vaccination records could be cost-effective, as well as promoting stringent use of antibiotics and a personalized approach to managing children with ILI.
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.
Introduction: Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed.
Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0–18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79).
Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.
Educating parents about the vaccination status of their children: A user-centered mobile application
(2017)
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.
To improve the identification and management of viral respiratory infections, we established a clinical and virologic surveillance program for pediatric patients fulfilling pre-defined case criteria of influenza-like illness and viral respiratory infections. The program resulted in a cohort comprising 6,073 patients (56% male, median age 1.6 years, range 0–18.8 years), where every patient was assessed with a validated disease severity score at the point-of-care using the ViVI ScoreApp. We used machine learning and agnostic feature selection to identify characteristic clinical patterns. We tested all patients for human adenoviruses, 571 (9%) were positive. Adenovirus infections were particularly common and mild in children ≥1 month of age but rare and potentially severe in neonates: with lower airway involvement, disseminated disease, and a 50% mortality rate (n = 2/4). In one fatal case, we discovered a novel virus …
Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0–18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (‘non-ICU’) versus management requiring ICU care (‘ICU’) added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.