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Serostatus testing and dengue vaccine cost-benefit thresholds.

ABSTRACT: The World Health Organization (WHO) currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a threshold modelling analysis, we identify settings where this guidance prohibits positive net-benefits, and are thus unfavourable. Generally, however, our model shows test-then-vaccinate strategies can improve CYD-TDV economic viability: effective testing reduces unnecessary vaccination costs while increasing health benefits. With sufficiently low testing cost, those trends outweigh additional screening costs, expanding the range of settings with positive net-benefits. This work highlights two aspects for further analysis of test-then-vaccinate strategies. We found that starting routine testing at younger ages could increase benefits; if real tests are shown to sufficiently address safety concerns, the manufacturer, regulators and WHO should revisit guidance restricting use to 9-years-and-older recipients. We also found that repeat testing could improve return-on-investment (ROI), despite increasing intervention costs. Thus, more detailed analyses should address questions on repeat testing and testing periodicity, in addition to real test sensitivity and specificity. Our results follow from a mathematical model relating ROI to epidemiology, intervention strategy, and costs for testing, vaccination and dengue infections. We applied this model to a range of strategies, costs and epidemiological settings pertinent to CYD-TDV. However, general trends may not apply locally, so we provide our model and analyses as an R package available via CRAN, denvax. To apply to their setting, decision-makers need only local estimates of age-specific seroprevalence and costs for secondary infections.

SUBMITTER: Pearson CAB

PROVIDER: S-EPMC6731500 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Serostatus testing and dengue vaccine cost-benefit thresholds.

Pearson Carl A B CAB Abbas Kaja M KM Clifford Samuel S Flasche Stefan S Hladish Thomas J TJ

Journal of the Royal Society, Interface 20190821 157

The World Health Organization (WHO) currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a threshold modelling analysis, we identify settings where this guidance prohibits positive net-benefits, and are thus unfavourable. Generally, however, our model shows test-then-vaccinate strategies can improve CYD-TDV economic viability: effective testing reduces unnecessary vaccination costs while increasing health benefits. With ...[more]

PMID: 31431184

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Project description:Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple disease parameters to evaluate protection by candidate vaccines.

Project description:BackgroundStimulated by the economic challenges faced by many sub-Saharan African countries and the changes in the rotavirus burden across these countries, this study aimed to inform the decision of health policy makers of eight sub-Saharan countries, who are yet to introduce the rotavirus vaccine as of Dec 31, 2020, on the health economic consequences of the introduction of the vaccine in terms of the costs and benefits.MethodsWe did a cost-benefit analysis using a simulation-based decision-analytic model for children aged younger than 1 year, who were followed up to 259 weeks, in the Central African Republic, Chad, Comoros, Equatorial Guinea, Gabon, Guinea, Somalia, and South Sudan. Data were collected and analysed between Jan 13, 2020, and Dec 11, 2020. Cost-effectiveness analysis and budget impact analysis were done as secondary analyses. Four rotavirus vaccinations (Rotarix, Rotateq, Rotavac, and Rotasiil) were compared with no vaccination. The primary outcome was disability-adjusted life-years averted, converted to monetary terms. The secondary outcomes include rotavirus gastroenteritis averted, and rotavirus vaccine-associated intussusception. The primary economic evaluation measure was the benefit-cost ratio (BCR).FindingsFor the modelling period, Jan 1, 2021, to Dec 31, 2030, we found that the benefits of introducing the rotavirus vaccine outweighed the costs in all eight countries, with Chad and the Central African Republic having the highest BCR of 19·42 and 11·36, respectively. Guinea had the lowest BCR of 3·26 amongst the Gavi-eligible countries. Equatorial Guinea and Gabon had a narrow BCR of 1·86 and 2·06, respectively. Rotarix was the optimal choice for all the Gavi-eligible countries; Rotasiil and Rotavac were the optimal choices for Equatorial Guinea and Gabon, respectively.InterpretationIntroducing the rotavirus vaccine in all eight countries, but with caution in Equatorial Guinea and Gabon, would be worthwhile. With the narrow BCR for Equatorial Guinea and Gabon, cautious, pragmatic, and stringent measures need to be employed to ensure optimal health benefits and cost minimisation of the vaccine introduction. The final decision to introduce the rotavirus vaccine should be preceded by comparing its BCR to the BCRs of other health-care projects.FundingCopenhagen Consensus Center and the Bill & Melinda Gates Foundation.

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Serostatus testing and dengue vaccine cost-benefit thresholds.

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Serostatus testing and dengue vaccine cost-benefit thresholds.

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