Summary The family Poxviridae currently comprises 22 genera that infect vertebrates. Of these, members of the Ortho‐ , Para‐ , Mollusci‐ and Yatapoxvirus genera have been associated with human diseases of high clinical relevance in dermatology. Historically, smallpox had been a notorious health threat until it was declared eradicated by the World Health Organization in 1979. Today, dermatologists are confronted with a variety of poxviral infections, such as farmyard pox, which occurs as a zoonotic infection after contact with animals. In the tropics, tanapox or vaccinia may be in the differential diagnosis as neglected tropical dermatoses. Molluscum contagiosum virus infection accounts for significant disease burden worldwide and is classified as a sexually transmitted infection in certain scenarios. Recently, mpox (monkeypox) has emerged as a public health emergency of international concern, requiring rapid recognition and appropriate management by dermatologists and infectious disease specialists. Advances and new insights into the epidemiology, diagnosis, clinical manifestations and complications, treatment, and prevention of poxviral infections require a high level of expertise and interdisciplinary skills from healthcare professionals linking virology, infectious diseases, and dermatology. This CME article provides a systematic overview and update to assist the practicing dermatologist in the identification, differential diagnosis, and management of poxviral infections.

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.

Zusammenfassung Die Familie Poxviridae umfasst derzeit 22 Gattungen, die Wirbeltiere infizieren können. Humanpathogene Pockenviren gehören den Gattungen Ortho‐ , Para‐ , Mollusci‐ und Yatapoxvirus an. Bis zur Eradikation der Variola vera im Jahr 1979 waren die Pocken, im Volksmund auch Blattern genannt, eine schwerwiegende Gesundheitsbedrohung für die Bevölkerung. Noch heute sind Dermatologen mit zahlreichen Pockenvirusinfektionen konfrontiert, wie den Bauernhofpocken, die als Zoonosen nach Tierkontakten in ländlichen Gebieten oder nach Massenversammlungen auftreten können. In den Tropen können Erkrankungen durch Tanapox‐ oder Vaccinia‐Viren zu den Differenzialdiagnosen gehören. Dellwarzen sind weltweit verbreitet und werden in bestimmten Fällen als sexuell übertragbare Pockenvirusinfektion angesehen. In jüngster Zeit hatten sich Mpox (Affenpocken) zu einer gesundheitlichen Notlage von internationaler Tragweite entwickelt, die eine rasche Identifizierung und angemessene Behandlung durch Dermatologen und Infektiologen erfordert. Fortschritte und neue Erkenntnisse über Epidemiologie, Diagnose, klinische Manifestationen und Komplikationen sowie Behandlung und Prävention von Pockenvirusinfektionen erfordern ein hohes Maß an Fachwissen und interdisziplinärer Zusammenarbeit in den Bereichen Virologie, Infektiologie und Dermatologie. Dieser CME‐Artikel bietet einen aktualisierten systematischen Überblick, um praktizierende Dermatologen bei der Identifizierung, Differenzialdiagnose und Behandlung klinisch relevanter Pockenvirusinfektionen zu unterstützen.

In July 2023, clade IIb-associated mpox reemerged in Germany at low levels, mainly affecting men who have sex with men. We report a representative case and phylogeny of available genome sequences. Our findings underscore the need for standardized surveillance and indication-based vaccination to limit transmission and help prevent endemicity.

The growing global emphasis on combating infectious diseases has highlighted the need for detailed analyses of outbreak patterns over time. Mpox, formerly known as monkeypox, remains a critical public health challenge in Nigeria, with significant outbreaks occurring between 2017 and 2024. Understanding the trends in Mpox cases, deaths, and geographical spread provides valuable insights into the effectiveness of public health interventions, regional disparities, and demographic vulnerabilities. These findings are essential for informing ongoing and future efforts to mitigate Mpox outbreaks and improve national outbreak preparedness. This study aims to analyze the progression of Mpox outbreaks in Nigeria, focusing on trends in confirmed and suspected cases, deaths, and geographic distribution across states from 2017 to 2024. Additionally, the study explores changes in age and gender-specific vulnerabilities, evaluates the impact of public health interventions, and assesses the reduction in disease burden between 2022 and 2024. A multi-faceted approach was employed, leveraging epidemiological data on Mpox cases from 2017 to 2024. Year-on-year comparisons of confirmed and suspected cases, fatalities, and their geographical distribution were performed to identify trends in disease progression and containment. Geospatial mapping techniques were used to examine regional disparities in Mpox case distribution. Demographic analysis explored shifts in age and gender vulnerabilities, while public health intervention outcomes were assessed based on reductions in cases and geographic spread. The comparative analysis from 2017 to 2024 revealed a significant 47% reduction in confirmed Mpox cases between 2023 and 2024, coupled with a notable decrease in both fatalities and geographic spread. Age-based analysis indicated a decline in disease vulnerability across younger age groups, while middle-aged males continued to show a relatively higher infection rate. A dramatic surge in cases occurred in 2022, with 762 confirmed cases, representing the peak of the outbreak. However, cases dropped significantly to 98 in 2023 and further to 40 in 2024, highlighting the success of recent public health interventions. Regional disparities remained evident, with certain states consistently showing higher case burdens, while others experienced reductions in cases, suggesting varied efficacy of local interventions. Geospatial analysis pinpointed persistent hotspots from 2017 to 2022, but a more contained spread was observed in 2023 and 2024. Additionally, gender analysis showed a consistent male predominance in cases across most age groups, with disparities becoming more pronounced in younger populations. The sharp reduction in Mpox cases and geographical spread from 2022 to 2024 reflects the positive impact of targeted public health interventions, including vaccination and containment strategies. However, persistent regional and gender disparities suggest that certain populations remain at higher risk, warranting continued monitoring and tailored interventions. Sustained efforts are necessary to prevent future outbreaks, maintain the progress achieved in reducing Mpox cases, and address the factors contributing to these disparities. To further reduce Mpox transmission and prevent future outbreaks, it is essential to strengthen disease surveillance systems in regions identified as consistent hotspots, ensuring rapid detection and response. Public health interventions should be tailored to address gender disparities, particularly the higher infection rates observed among males, while expanding vaccination campaigns and health education initiatives in high-burden areas. Additionally, targeted efforts must investigate the behavioral and biological factors contributing to male vulnerability, especially among younger populations. Sustained focus on these strategies will be critical to maintaining the progress achieved and closing the gaps in disease control. This study provides a comprehensive, multi-year analysis of Mpox outbreaks in Nigeria, offering critical insights into the effectiveness of public health interventions, regional disparities, and demographic trends. The findings underscore the importance of geospatial data in understanding disease distribution and controlling infectious outbreaks. The significant case reduction from 2022 to 2024 highlights the success of ongoing public health measures, while also emphasizing the need for continuous monitoring and adaptive strategies to maintain and further improve disease control.

Encephalitis and acute disseminated encephalomyelitis (ADEM) are often caused or triggered by viruses—but the specific pathogen commonly remains unidentified in routine care. We explored the use of viral metagenomic next-generation sequencing (mNGS) in addition to PCR testing of non-invasive stool samples to see if unbiased testing could potentially increase diagnostic yield. To identify specific clinical cases at the point of care, we took advantage of a previously published digital app allowing instant clinical case classification based on consensus case criteria, the VACC-Tool. This hospital-based prospective digital surveillance program assessed 100 pediatric patients (mean age: 11 years, range: 0.15–17.85; 49% male) with case-confirmed encephalitis and/or ADEM. Analysis of case classification at the point of care revealed that in routine care, 96% of confirmed encephalitis/ADEM cases had been missed. Overall agreement of routine care diagnoses with digital encephalitis/ADEM case classification was <50%. Also in routine care, only 13% of cases held a virus-related diagnosis, i.e., herpesvirus (n = 8) and enterovirus infection (n = 5). Use of mNGS increased the yield of virus detection by 77% (n = 23 virus hits). Specifically, mNGS identified 10 additional virus species beyond herpes- and enteroviruses. Of the additional 23 virus hits detected with mNGS, PCR confirmation was possible post hoc in 14 cases (61%). Linking digital case classification, mNGS, and PCR testing may not be feasible in routine care at this point but may help to provide hints to the pathogenesis of encephalitis/ADEM in childhood, warranting further research and exploration.

In July 2023, clade IIb-associated mpox reemerged in Germany at low levels, mainly affecting men who have sex with men. We report a representative case and phylogeny of available genome sequences. Our findings underscore the need for standardized surveillance and indication-based vaccination to limit transmission and help prevent endemicity.

In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.

To improve the identification andmanagement 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: HAdV-80. Standardized surveillance leveraging digital technology helps to identify characteristic clinical patterns, risk factors, and emerging pathogens.

Influenza virus (IV) coinfection, i.e., simultaneous infection with IV and other viruses, is a common occurrence in humans. However, little is known about the incidence and clinical impact of coinfection with two different IV subtypes or lineages ("dual infections"). We report the incidence, standardized disease severity, and follow-up of IV dual infections from a hospital-based digital surveillance cohort, comprising 6073 pediatric patients fulfilling pre-defined criteria of influenza-like illness in Berlin, Germany. All patients were tested for IV A/B by PCR, including subtypes/lineages. We assessed all patients at the bedside using the mobile ViVI ScoreApp, providing a validated disease severity score in real-time. IV-positive patients underwent follow-up assessments until resolution of symptoms. Overall, IV dual infections were rare (4/6073 cases; 0.07%, incidence 12/100,000 per year) but showed unusual and/or prolonged clinical presentations with slightly above-average disease severity. We observed viral rebound, serial infection, and B/Yamagata-B/Victoria dual infection. Digital tools, used for instant clinical assessments at the bedside, combined with baseline/follow-up virologic investigation, help identify coinfections in cases of prolonged and/or complicated course of illness. Infection with one IV does not necessarily prevent consecutive or simultaneous (co-/dual) infection, highlighting the importance of multivalent influenza vaccination and enhanced digital clinical and virological surveillance.

Currently, 88 different Human Adenovirus (HAdV) types are grouped into seven HAdV species A to G. Most types (57) belong to species HAdV-D. Recombination between capsid genes (hexon, penton and fiber) is the main factor contributing to the diversity in species HAdV-D. Noteworthy, species HAdV-C contains so far only five types, although species HAdV-C is highly prevalent and clinically significant in immunosuppressed patients. Therefore, the evolution of species HAdV-C was studied by generating 51 complete genome sequences from circulating strains. Clustering of the whole genome HAdV-C sequences confirmed classical typing results (fifteen HAdV-C1, thirty HAdV-C2, four HAdV-C5, two HAdV-C6). However, two HAdV-C2 strains had a novel penton base sequence and thus were re-labeled as the novel type HAdV-C89. Fiber and early gene region 3 (E3) sequences clustered always with the corresponding prototype sequence but clustering of the E4 region indicated recombination events in 26 out of the 51 sequenced specimens. Recombination of the E1 gene region was detected in 16 circulating strains. As early gene region sequences are not considered in the type definition of HAdVs, evolution of HAdV-C remains on the subtype level. Nonetheless, recombination of the E1 and E4 gene regions may influence the virulence of HAdV-C strains.

ABSTRACT Human parechoviruses (HPeV) circulate worldwide, causing a broad variety of symptoms, preferentially in early childhood. We report here the nearly complete genome sequence of a novel HPeV type, consisting of 7,062 nucleotides and encoding 2,179 amino acids. M36/CI/2014 was taxonomically classified as HPeV-17 by the picornavirus study group.

Background Infants exhibit elevated influenza virus loads and prolonged viral shedding, which may increase the risk for resistance development, especially in cases of suboptimal exposure to antiviral therapy. Methods We performed a prospective surveillance of hospitalized infants undergoing oseltamivir therapy during the 2008–2009 and 2011–2012 influenza seasons at two paediatric hospitals in Germany. A total of 37 infants less than 1 year of age with laboratory confirmed influenza A(H3N2) infection received oseltamivir as per physician's order for 5 days (2008–2009 season: 2 mg/kg twice daily; 2011–2012 season: 2.0 mg/kg; 2.5 mg/kg and 3.0 mg/kg twice daily for infants <1 month; 2–3 months and 4–12 months, respectively). Virus load, the susceptibility to neuraminidase inhibitors (NAIs), and the presence of molecular markers of resistance to NAIs was assessed for influenza viruses recovered from respiratory samples collected at baseline and during follow-up visits. Results Overall, 73% of the infants continued to shed viral RNA detectable by reverse transcription (RT)-PCR after dose number 10 of oseltamivir; 12 infants shed viruses, 2 of them (both 9 months of age) shed resistant viruses. Resistance was characterized by ≥1,000-fold increase of 50% inhibitory concentration (IC50) for oseltamivir, up to 50-fold for zanamivir and elevated Km values when compared to susceptible A(H3N2) strains. Sanger sequencing revealed the selection of the NA-R292K substitution in both instances (after dose number 10 on day 6). Conclusions Our data suggest that it may be relevant to monitor antiviral resistance systematically in all infants, considering that the European Medicines Agency has recently extended the licensure for oseltamivir to include full-term infants.

ABSTRACT 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.

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.

Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). Methods: The surveillance was conducted at the Charité Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Results: Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. Conclusions: We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.

Infectious and inflammatory diseases of the central nervous system are difficult to identify early. Case definitions for aseptic meningitis, encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM) are available, but rarely put to use. The VACC-Tool (Vienna Vaccine Safety Initiative Automated Case Classification-Tool) is a mobile application enabling immediate case ascertainment based on consensus criteria at the point-of-care. The VACC-Tool was validated in a quality management program in collaboration with the Robert-Koch-Institute. Results were compared to ICD-10 coding and retrospective analysis of electronic health records using the same case criteria. Of 68,921 patients attending the emergency room in 10/2010–06/2013, 11,575 were hospitalized, with 521 eligible patients (mean age: 7.6years) entering the quality management program. Using the VACC-Tool at the point-of-care, 180/521 cases were classified successfully and 194/521 ruled out with certainty. Of the 180 confirmed cases, 116 had been missed by ICD-10 coding, 38 misclassified. By retrospective application of the same case criteria, 33 cases were missed. Encephalitis and ADEM cases were most likely missed or misclassified. The VACC-Tool enables physicians to ask the right questions at the right time, thereby classifying cases consistently and accurately, facilitating translational research. Future applications will alert physicians when additional diagnostic procedures are required.