scholarly journals An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections

2016 ◽  
Author(s):  
T. Alex Perkins ◽  
Robert C. Reiner ◽  
Guido España ◽  
Quirine A. ten Bosch ◽  
Amit Verma ◽  
...  
Keyword(s):  
Public Health ◽  
Dengue Virus ◽  
Vaccine Efficacy ◽  
Denv Infection ◽  
Health Impact ◽  
Public Health Impact ◽  
Statistical Uncertainty ◽  
Dengue Vaccine ◽  
Agent Based ◽  
Biological Uncertainty

ABSTRACTGiven the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia® from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) “statistical uncertainty” about the numerical value of the vaccine’s efficacy against disease, and (2) “biological uncertainty” about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia® took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccine’s public health impact.

scholarly journals Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure

2018 ◽  
Author(s):  
Guido España ◽  
Yutong Yao ◽  
Kathryn B. Anderson ◽  
Meagan C. Fitzpatrick ◽  
David L. Smith ◽  
...  
Keyword(s):  
Public Health ◽  
Cost Effectiveness ◽  
Dengue Virus ◽  
Health Impact ◽  
The Philippines ◽  
Public Health Impact ◽  
Dengue Vaccine ◽  
Serological Screening ◽  
Serological Assay ◽  
High Transmission

ABSTRACTThe tetravalent dengue vaccine CYD-TDV (Dengvaxia®) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting).AUTHOR SUMMARYAmong several viral diseases transmitted by Aedes aegypti mosquitoes, dengue imposes the greatest and most persistent burden on global health. Efforts to curb its spread would benefit greatly from the availability of an effective vaccine. Currently, the only licensed dengue vaccine, known as CYD-TDV or by the brand name Dengvaxia®, is only recommended for use in people who are known to have been exposed to dengue virus in the past. Because symptoms of dengue can range from severe to mild to imperceptible, using clinical history alone to assess whether a person was previously exposed is unreliable. Instead, serological assays, which measure a person’s immune response to dengue virus, are necessary to confirm whether a person was previously exposed. Because serological assays can be subject to substantial error, we used a simulation model to assess how impactful CYD-TDV vaccination would be under different scenarios about the accuracy of a serological assay and the intensity of transmission in a given area. We found that the health impact and cost-effectiveness of CYD-TDV vaccination depended on the accuracy of the serological assay, its cost, and the setting in which it is deployed.

scholarly journals Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against DENV-2 and -4

2018 ◽  
Vol 92 (12) ◽  
pp. e00440-18 ◽  
Author(s):  
Veronique Barban ◽  
Nathalie Mantel ◽  
Aymeric De Montfort ◽  
Anke Pagnon ◽  
Fabrine Pradezynski ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Clinical Efficacy ◽  
Nonhuman Primate ◽  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Denv Infection ◽  
Dengue Vaccine ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Translational Approach

ABSTRACTRecent data obtained with the live-attenuated tetravalent dengue CYD-TDV vaccine showed higher protective efficacy against dengue virus type 4 (DENV-4) than against DENV-2. In contrast, results from previous studies in nonhuman primates predicted comparable high levels of protection against each serotype. Maximum viral loads achieved in macaques by subcutaneous inoculation of DENV are generally much lower than those observed in naturally dengue virus-infected humans. This may contribute to an overestimation of vaccine efficacy. Using more-stringent DENV infection conditions consisting of the intravenous inoculation of 10750% cell culture infectious doses (CCID50) in CYD-TDV-vaccinated macaques, complete protection (i.e., undetectable viral RNA) was achieved in all 6 monkeys challenged with DENV-4 and in 6/18 of those challenged with DENV-2, including transiently positive animals. All other infected macaques (12/18) developed sustained DENV-2 RNAemia (defined as detection of viral RNA in serum samples) although 1 to 3 log10units below the levels achieved in control animals. Similar results were obtained with macaques immunized with either CYD-TDV or monovalent (MV) CYD-2. This suggests that partial protection against DENV-2 was mediated mainly by CYD-2 and not by the other CYDs. Postchallenge induction of strong anamnestic responses, suggesting efficient vaccine priming, likely contributed to the reduction of DENV-2 RNAemia. Finally, an inverse correlation between DENV RNA titers postchallenge and vaccine-induced homotypic neutralizing antibody titers prechallenge was found, emphasizing the key role of these antibodies in controlling DENV infection. Collectively, these data show better agreement with reported data on CYD-TDV clinical vaccine efficacy against DENV-2 and DENV-4. Despite inherent limitations of the nonhuman primate model, these results reinforce its value in assessing the efficacy of dengue vaccines.IMPORTANCEThe nonhuman primate (NHP) model is the most widely recognized tool for assessing the protective activity of dengue vaccine candidates, based on the prevention of postinfection DENV viremia. However, its use has been questioned after the recent CYD vaccine phase III trials, in which moderate protective efficacy against DENV-2 was reported, despite full protection against DENV-2 viremia previously being demonstrated in CYD-vaccinated monkeys. Using a reverse translational approach, we show here that the NHP model can be improved to achieve DENV-2 protection levels that show better agreement with clinical efficacy. With this new model, we demonstrate that the injection of the CYD-2 component of the vaccine, in either a monovalent or a tetravalent formulation, is able to reduce DENV-2 viremia in all immunized animals, and we provide clear statistical evidence that DENV-2-neutralizing antibodies are able to reduce viremia in a dose-dependent manner.

Public Health Impact of Substance Use on Adolescent: A Snapshot of Yenagoa in Bayelsa State. Nigeria

2019 ◽  
Author(s):  
Morufu Raimi ◽  
Abdulraheem Aishat Funmilayo ◽  
Iteimowei Major ◽  
Okoyen Ebikapaye ◽  
Olaolu Oyinlola Bilewu
Keyword(s):  
Public Health ◽  
Substance Use ◽  
Health Impact ◽  
Public Health Impact
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