Economic Value of Dengue Vaccine in Thailand

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of$60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of$200. When the total vaccine series was $1.50, many scenarios were cost saving

Cost and disease burden of Dengue in Cambodia

<p>Abstract</p> <p>Background</p> <p>Dengue is endemic in Cambodia (pop. estimates 14.4 million), a country with poor health and economic indicators. Disease burden estimates help decision makers in setting priorities. Using recent estimates of dengue incidence in Cambodia, we estimated the cost of dengue and its burden using disability adjusted life years (DALYs).</p> <p>Methods</p> <p>Recent population-based cohort data were used to calculate direct and productive costs, and DALYs. Health seeking behaviors were taken into account in cost estimates. Specific age group incidence estimates were used in DALYs calculation.</p> <p>Results</p> <p>The mean cost per dengue case varied from US$36 -$75 over 2006-2008 respectively, resulting in an overall annual cost from US$3,327,284 in 2008 to US$14,429,513 during a large epidemic in 2007. Patients sustain the highest share of costs by paying an average of 78% of total costs and 63% of direct medical costs. DALY rates per 100,000 individuals ranged from 24.3 to 100.6 in 2007-2008 with 80% on average due to premature mortality.</p> <p>Conclusion</p> <p>Our analysis confirmed the high societal and individual family burden of dengue. Total costs represented between 0.03 and 0.17% of Gross Domestic Product. Health seeking behavior has a major impact on costs. The more accurate estimate used in this study will better allow decision makers to account for dengue costs particularly among the poor when balancing the benefits of introducing a potentially effective dengue vaccine.</p

High Dengue Case Capture Rate in Four Years of a Cohort Study in Nicaragua Compared to National Surveillance Data

Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development

Relativistic two-photon and two-gluon decay rates of heavy quarkonia

The decay rates of $c\bar{c}$ and $b\bar{b}$ through two-photon or two-gluon annihilations are obtained by using totally relativistic decay amplitudes and a sophisticated quantum-chromodynamic potential model for heavy quarkonia. Our results for the photonic and gluonic widths of the 1S0, 3P0, and the 3P2 states are in excellent agreement with the available experimental data. The procedures and mathematical techniques used by us for the treatment of the fermion-antifermion bound states are also applicable to other decay processes.Comment: 15 pages, RevTeX, PostScript available at http://gluon.physics.wayne.edu/wsuhep/jim/predecay.p

Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

Patients with severe dengue illness typically develop complications in the later stages of illness, making early clinical management of all patients with suspected dengue infection difficult. An early prediction tool to identify which patients will have a severe dengue illness will improve the utilization of limited hospital resources in dengue endemic regions. We performed classification and regression tree (CART) analysis to establish predictive algorithms of severe dengue illness. Using a Thai hospital pediatric cohort of patients presenting within the first 72 hours of a suspected dengue illness, we developed diagnostic decision algorithms using simple clinical laboratory data obtained on the day of presentation. These algorithms correctly classified near 100% of patients who developed a severe dengue illness while excluding upwards of 50% of patients with mild dengue or other febrile illnesses. Our algorithms utilized white blood cell counts, percent white blood cell differentials, platelet counts, elevated aspartate aminotransferase, hematocrit, and age. If these algorithms can be validated in other regions and age groups, they will help in the clinical management of patients with suspected dengue illness who present within the first three days of fever onset

Improving guideline adherence for cardiac rehabilitation in the Netherlands

Background In 2004, the Netherlands Society of Cardiology released the current guideline on cardiac rehabilitation. Given its complexity and the involvement of various healthcare disciplines, it was supplemented with a clinical algorithm, serving to facilitate its implementation in daily practice. Although the algorithm was shown to be effective for improving guideline adherence, several shortcomings and deficiencies were revealed. Based on these findings, the clinical algorithm has now been updated. This article describes the process and the changes that were made. Methods The revision consisted of three phases. First, the reliability of the measurement instruments included in the 2004 Clinical Algorithm was investigated by evaluating between-centre variations of the baseline assessment data. Second, based on the available evidence, a multidisciplinary expert advisory panel selected items needing revision and provided specific recommendations. Third, a guideline development group decided which revisions were finally included, also taking practical considerations into account. Results A total of nine items were revised: three because of new scientific insights and six because of the need for more objective measurement instruments. In all revised items, subjective assessment methods were replaced by more objective assessment tools (e.g. symptom-limited exercise instead of clinical judgement). In addition, four new key items were added: screening for anxiety/depression, stress, cardiovascular risk profile and alcohol consumption. Conclusion Based on previously determined shortcomings, the Clinical Algorithm for Cardiac Rehabilitation was thoroughly revised mainly by incorporating more objective assessment methods and by adding several new key area

Analysis of RNA Binding by the Dengue Virus NS5 RNA Capping Enzyme

Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase activity is currently unknown, and how the capping enzyme binds its diphosphorylated RNA substrate is important for deciphering how the flavivirus guanylyltransferase functions. In this report we examine how flavivirus NS5 N-terminal capping enzymes bind to the 5′ end of the viral RNA using a fluorescence polarization-based RNA binding assay. We observed that the KD for RNA binding is approximately 200 nM Dengue, Yellow Fever, and West Nile virus capping enzymes. Removal of one or both of the 5′ phosphates reduces binding affinity, indicating that the terminal phosphates contribute significantly to binding. RNA binding affinity is negatively affected by the presence of GTP or ATP and positively affected by S-adensyl methoninine (SAM). Structural superpositioning of the dengue virus capping enzyme with the Vaccinia virus VP39 protein bound to RNA suggests how the flavivirus capping enzyme may bind RNA, and mutagenesis analysis of residues in the putative RNA binding site demonstrate that several basic residues are critical for RNA binding. Several mutants show differential binding to 5′ di-, mono-, and un-phosphorylated RNAs. The mode of RNA binding appears similar to that found with other methyltransferase enzymes, and a discussion of diphosphorylated RNA binding is presented

Consumer Willingness to Pay for Dengue Vaccine (CYD-TDV, Dengvaxia®) in Brazil; Implications for Future Pricing Considerations

Introduction and Objective: Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur. However, given that the vaccine will potentially be paid via the public health system, information is need regarding consumers’ willingness to pay for the dengue vaccine in the country as well as discussions related to the possible inclusion of this vaccine into the public health system. This was the objective of this research. Methods: We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Results: 507 individuals were interviewed. These were mostly female (62.4%) had completed high school (62.17%), were working (74.4%), had private health insurance (64.5%) and did not have dengue (67.4%). The maximum median value of consumers’ willingness to pay for CYD-TDV vaccine is US$33.61 (120.00BRL) for the complete schedule and US$11.20 (40.00BRL) per dose. At the price determined by the Brazil’s regulatory chamber of pharmaceutical products market for the commercialization of Dengvaxia(®) for three doses, only 17% of the population expressed willingness to pay for this vaccine. Conclusion: Brazil is currently one of the largest markets for dengue vaccine and the price established is a key issue. We believe the manufacturer should asses the possibility of lower prices to reach a larger audience among the Brazilian population

Modeling Transmission Dynamics and Control of Vector-Borne Neglected Tropical Diseases

Neglected tropical diseases affect more than one billion people worldwide. The populations most impacted by such diseases are typically the most resource-limited. Mathematical modeling of disease transmission and cost-effectiveness analyses can play a central role in maximizing the utility of limited resources for neglected tropical diseases. We review the contributions that mathematical modeling has made to optimizing intervention strategies of vector-borne neglected diseases. We propose directions forward in the modeling of these diseases, including integrating new knowledge of vector and pathogen ecology, incorporating evolutionary responses to interventions, and expanding the scope of sensitivity analysis in order to achieve robust results