Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study.

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.

Consultations for Influenza-Like Illness in Primary Care in The Netherlands: A Regression Approach.

OBJECTIVES: To estimate the general practitioner (GP) consultation rate attributable to influenza in The Netherlands. METHODS: Regression analysis was performed on the weekly numbers of influenza-like illness (ILI) GP consultations and laboratory reports for influenza virus types A and B and 8 other pathogens over the period 2003-2014 (11 influenza seasons; week 40-20 of the following year). RESULTS: In an average influenza season, 27% and 11% of ILI GP consultations were attributed to infection by influenza virus types A and B, respectively. Influenza is therefore responsible for approximately 107 000 GP consultations (651/100 000) each year in The Netherlands. GP consultation rates associated with influenza infection were highest in children under 5 years of age, at 667 of 100 000 for influenza A and 258 of 100 000 for influenza B. Influenza virus infection was found to be the predominant cause of ILI-related GP visits in all age groups except children under 5, in which respiratory syncytial virus (RSV) infection was found to be the main contributor. CONCLUSIONS: The burden of influenza in terms of GP consultations is considerable. Overall, influenza is the main contributor to ILI. Although ILI symptoms in children under 5 years of age are most often associated with RSV infection, the majority of visits related to influenza occur among children under 5 years of age.

[The sustainability of the health system and the pharmaceutical market: A permanent interaction between the cost of medications, the patent system, and disease care]. / La sostenibilidad del sistema de salud y el mercado farmacéutico: Una interacción permanente entre el costo de los medicamentos, el sistema de patentes y la atención a las enfermedades.

Taking into account the latent threat of future pandemics, the objective of this study is to analyze - particularly with respect to medications - the sustainability of the health system, healthcare coverage, budgetary efficiency, and connections with the pharmaceutical patent system. In this context, the pharmaceutical patent system acts as a determining factor, given that promoting its existence stimulates the production of research, but in turn its existence stands in the way of rapid advancements, primarily due to the development of protective legislation concerning patents, which has largely accommodated the industry. Given that the pharmaceutical industry has managed to extend the duration of patents and avoid the incorporation of generics, our analysis focuses on the influence of pharmaceutical patents; this influence has led to reflection on the possibility of combining efforts by forging alliances between numerous companies and the public sector in order to face the challenges posed by new diseases caused by viruses that give rise to epidemics and pandemics.

Ante la amenaza latente de futuras pandemias, este estudio tiene como objetivo analizar ­desde el eje de los medicamentos­ la sostenibilidad del sistema sanitario, la cobertura, la eficiencia del gasto y su vinculación al sistema de patentes farmacéuticas. En este marco, el sistema de patentes farmacéuticas adquiere un papel determinante, dado que fomentar su existencia estimula la producción de investigación pero, a su vez, su existencia no suscita un rápido avance, debido al desarrollo legislativo protector que han tenido las patentes y que ha dado lugar a un acomodamiento de la industria. Como la industria farmacéutica ha conseguido extender la duración de patentes y evitar la incorporación de genéricos, se analiza la influencia de las patentes farmacéuticas que ha dado lugar a reflexionar acerca de la posibilidad de consorciar esfuerzos realizando alianzas entre varias empresas y el sector público para afrontar los retos que plantean nuevas enfermedades producidas por virus que dan lugar a epidemias y pandemias.

Costs and benefits of interventions aimed at major infectious disease threats: lessons from the literature.

Pandemics and major outbreaks have the potential to cause large health losses and major economic costs. To prioritize between preventive and responsive interventions, it is important to understand the costs and health losses interventions may prevent. We review the literature, investigating the type of studies performed, the costs and benefits included, and the methods employed against perceived major outbreak threats. We searched PubMed and SCOPUS for studies concerning the outbreaks of SARS in 2003, H5N1 in 2003, H1N1 in 2009, Cholera in Haiti in 2010, MERS-CoV in 2013, H7N9 in 2013, and Ebola in West-Africa in 2014. We screened titles and abstracts of papers, and subsequently examined remaining full-text papers. Data were extracted according to a pre-constructed protocol. We included 34 studies of which the majority evaluated interventions related to the H1N1 outbreak in a high-income setting. Most interventions concerned pharmaceuticals. Included costs and benefits, as well as the methods applied, varied substantially between studies. Most studies used a short time horizon and did not include future costs and benefits. We found substantial variation in the included elements and methods used. Policymakers need to be aware of this and the bias toward high-income countries and pharmaceutical interventions, which hampers generalizability. More standardization of included elements, methodology, and reporting would improve economic evaluations and their usefulness for policy.

Longitudinal profiling of the vaccination coverage in Brazil reveals a recent change in the patterns hallmarked by differential reduction across regions.

OBJECTIVE: Vaccination coverage is decreasing worldwide, favoring the potential reemergence of vaccine-preventable diseases. In this study, we performed a longitudinal characterization of vaccination coverage in Brazil and compared the profiles between the distinct regions in the country to test whether there has been a substantial change over the last 5 years. METHODS: De-identified publicly available data were retrieved from the repository of the Brazilian Ministry of Health, comprising detailed information on vaccination coverage in all age groups between 1994 and 2019. The vaccination coverage for the whole country and for each Brazilian region, by year, was examined, and a time-series pattern analysis was performed. RESULTS: A significant decrease in overall vaccination coverage across the country regions was observed between 2017 and 2019, especially in childhood immunization. A reduction in BCG, hepatitis B, influenza, and rotavirus vaccine coverage was observed. Conversely, vaccines against measles, mumps, rubella, varicella, and meningococcus showed an increase in coverage. Region-specific changes in vaccination patterns within the study period were observed. CONCLUSIONS: A substantial reduction in vaccination coverage was detected in Brazil, a country already highly susceptible to the emergence of epidemic infectious diseases. Continuing evaluation of the immunization program actions may help to improve vaccination coverage and prevent new epidemics.

La sostenibilidad del sistema de salud y el mercado farmacéutico: Una interacción permanente entre el costo de los medicamentos, el sistema de patentes y la atención a las enfermedades / The sustainability of the health system and the pharmaceutical market: A permanent interaction between the cost of medications, the patent system, and disease care

RESUMEN Ante la amenaza latente de futuras pandemias, este estudio tiene como objetivo analizar -desde el eje de los medicamentos- la sostenibilidad del sistema sanitario, la cobertura, la eficiencia del gasto y su vinculación al sistema de patentes farmacéuticas. En este marco, el sistema de patentes farmacéuticas adquiere un papel determinante, dado que fomentar su existencia estimula la producción de investigación pero, a su vez, su existencia no suscita un rápido avance, debido al desarrollo legislativo protector que han tenido las patentes y que ha dado lugar a un acomodamiento de la industria. Como la industria farmacéutica ha conseguido extender la duración de patentes y evitar la incorporación de genéricos, se analiza la influencia de las patentes farmacéuticas que ha dado lugar a reflexionar acerca de la posibilidad de consorciar esfuerzos realizando alianzas entre varias empresas y el sector público para afrontar los retos que plantean nuevas enfermedades producidas por virus que dan lugar a epidemias y pandemias.

ABSTRACT Taking into account the latent threat of future pandemics, the objective of this study is to analyze - particularly with respect to medications - the sustainability of the health system, healthcare coverage, budgetary efficiency, and connections with the pharmaceutical patent system. In this context, the pharmaceutical patent system acts as a determining factor, given that promoting its existence stimulates the production of research, but in turn its existence stands in the way of rapid advancements, primarily due to the development of protective legislation concerning patents, which has largely accommodated the industry. Given that the pharmaceutical industry has managed to extend the duration of patents and avoid the incorporation of generics, our analysis focuses on the influence of pharmaceutical patents; this influence has led to reflection on the possibility of combining efforts by forging alliances between numerous companies and the public sector in order to face the challenges posed by new diseases caused by viruses that give rise to epidemics and pandemics.

Persistent socioeconomic and racial and ethnic disparities in pathogen burden in the United States, 1999-2014.

The disproportionate burden of prevalent, persistent pathogens among disadvantaged groups may contribute to socioeconomic and racial/ethnic disparities in long-term health. We assessed if the social patterning of pathogen burden changed over 16 years in a U.S.-representative sample. Data came from 17 660 National Health and Nutrition Examination Survey participants. Pathogen burden was quantified by summing the number of positive serologies for cytomegalovirus, herpes simplex virus-1, HSV-2, human papillomavirus and Toxoplasma gondii and dividing by the number of pathogens tested, giving a percent-seropositive for each participant. We examined sex- and age-adjusted mean pathogen burdens from 1999-2014, stratified by race/ethnicity and SES (poverty-to-income ratio (PIR); educational attainment). Those with a PIR < 1.3 had a mean pathogen burden 1.4-1.8 times those with a PIR > 3.5, with no change over time. Educational disparities were even greater and showed some evidence of increasing over time, with the mean pathogen burden among those with less than a high school education approximately twice that of those who completed more than high school. Non-Hispanic Black, Mexican American and other Hispanic participants had a mean pathogen burden 1.3-1.9 times non-Hispanic Whites. We demonstrate that socioeconomic and racial/ethnic disparities in pathogen burden have persisted across 16 years, with little evidence that the gap is closing.

Virology Tests in Brain-Dead Donors: Let the Bills Run Up?

OBJECTIVES: In the organ donation process, screening for serologic markers for a selection of agents is essential to prevent infection transmission. The screening of donors for specific potential infections can never absolutely exclude the risk of transmission. For reevaluation of serology tests, we analyzed results of tests requested for all brain-dead donors. MATERIALS AND METHODS: Our study included all actual brain-dead donors who were seen from January 2017 to February 2018, received ancillary tests, and had final confirmation of brain death at our organ procurement unit. RESULTS: Most candidates for organ and tissue donation were seronegative for intended agents. We found that 14.4% of the samples were suspicious for infectious and needed further evaluation; 12.2% of donors had positive results corresponding to hepatitis B, and only 1.9% were rejected from donation. Requisiteness to DNA detection for hepatitis B virus infection was mainly related to age over 50 years. CONCLUSIONS: The process of donor screening must systemically assess the donor. At the final stage, essential biomarkers must be investigated. Application of more caution in evaluation of older donors, including more screening tests before transfer to the operating room, remains mandatory.

Consequences of Pathogen Lists: Why Some Diseases May Continue to Plague Us.

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.

Systematic review of the incremental costs of interventions that increase immunization coverage.

Achieving and maintaining high vaccination coverage requires investments, but the costs and effectiveness of interventions to increase coverage remain poorly characterized. We conducted a systematic review of the literature to identify peer-reviewed studies published in English that reported interventions aimed at increasing immunization coverage and the associated costs and effectiveness of the interventions. We found limited information in the literature, with many studies reporting effectiveness estimates, but not providing cost information. Using the available data, we developed a cost function to support future programmatic decisions about investments in interventions to increase immunization coverage for relatively low and high-income countries. The cost function estimates the non-vaccine cost per dose of interventions to increase absolute immunization coverage by one percent, through either campaigns or routine immunization. The cost per dose per percent increase in absolute coverage increased with higher baseline coverage, demonstrating increasing incremental costs required to reach higher coverage levels. Future studies should evaluate the performance of the cost function and add to the database of available evidence to better characterize heterogeneity in costs and generalizability of the cost function.

The state of gene therapy research in Africa, its significance and implications for the future.

Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV-1, hepatitis B virus and Ebola virus, which are of significant public health importance in Africa. Although enthusiasm for gene therapy is justified, significant challenges to implementing the technology remain. These include ensuring efficient delivery of therapeutic nucleic acids to target cells, limiting unintended effects, cost and complexity of treatment regimens. In addition, implementation of effective legislation that will govern gene therapy research will be a challenge. Nevertheless, it is an exciting prospect that gene therapy should soon reach the mainstream of medical management. Participation of African researchers in the exciting developments is currently limited, but their involvement is important to address health problems, develop capacity and enhance economic progress of the continent.

Factors of Concern Regarding Zika and Other Aedes aegypti-Transmitted Viruses in the United States.

The recent explosive outbreaks of Zika and chikungunya throughout the Americas has raised concerns about the threats that these and similar diseases may pose to the United States (U.S.). The commonly accepted association between tropical climates and the endemicity of these diseases has led to concerns about the possibility of their redistribution due to climate change and transmission arising from cases imported from endemic regions initiating outbreaks in the United States. While such possibilities are indeed well founded, the analysis of historical records not only confirms the potential critical role of traveling and globalization but also reveals that the climate in the United States currently is suitable for local transmission of these viruses. Thus, the main factors preventing these diseases from occurring in the United States today are more likely socioeconomic such as lifestyle, housing infrastructure, and good sanitation. As long as such conditions are maintained, it seems unlikely that local transmission will occur to any great degree, particularly in the northern states. Indeed, a contributing factor to explain the current endemicity of these diseases in less-developed American countries may be well explained by socioeconomic and some lifestyle characteristics in such countries.

Epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany: a systematic review.

OBJECTIVES: Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. The objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany. METHODS: We systematically reviewed studies published since 2000. The literature search was conducted using PubMed and EMBASE. Also, we used German notification data to give an up-to-date overview of the epidemiology of the four diseases under consideration. RESULTS: Thirty-six studies were included in our review. Results suggest that there is still considerable morbidity due to childhood diseases in Germany. Studies providing cost estimates are scarce. Comparative analyses of different data sources (notification data vs. claims data) revealed a potential underestimation of incidence estimates when using notification data. Furthermore, several studies showed regional differences in incidence of some of the diseases under consideration. CONCLUSIONS: Our findings underline the need for improved vaccination and communication strategies targeting all susceptible age and risk groups on a national and local level.